---
_id: '14363'
abstract:
- lang: eng
text: Mitochondrial networks remodel their connectivity, content, and subcellular
localization to support optimized energy production in conditions of increased
environmental or cellular stress. Microglia rely on mitochondria to respond to
these stressors, however our knowledge about mitochondrial networks and their
adaptations in microglia in vivo is limited. Here, we generate a mouse model that
selectively labels mitochondria in microglia. We identify that mitochondrial networks
are more fragmented with increased content and perinuclear localization in vitro
vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the
injury site after optic nerve crush. Preventing microglial UCP2 increase after
injury by selective knockout induces cellular stress. This results in mitochondrial
hyperfusion in male microglia, a phenotype absent in females due to circulating
estrogens. Our results establish the foundation for mitochondrial network analysis
of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects
of microglia in other pathologies.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Scientific Service Units (SSU) of ISTA through resources
provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF),
and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael
Schunn for excellent mouse colony management and support. This research was supported
by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John
A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback
on the project and article.
article_number: '107780'
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Felix
full_name: Sternberg, Felix
last_name: Sternberg
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Elena E.
full_name: Pohl, Elena E.
last_name: Pohl
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations
of microglia reveal sex-specific stress response after injury and UCP2 knockout.
iScience. 2023;26(10). doi:10.1016/j.isci.2023.107780
apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino,
A., Pohl, E. E., & Siegert, S. (2023). Mitochondrial network adaptations of
microglia reveal sex-specific stress response after injury and UCP2 knockout.
IScience. Elsevier. https://doi.org/10.1016/j.isci.2023.107780
chicago: Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg,
Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network
Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and
UCP2 Knockout.” IScience. Elsevier, 2023. https://doi.org/10.1016/j.isci.2023.107780.
ieee: M. E. Maes et al., “Mitochondrial network adaptations of microglia
reveal sex-specific stress response after injury and UCP2 knockout,” iScience,
vol. 26, no. 10. Elsevier, 2023.
ista: Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE,
Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific
stress response after injury and UCP2 knockout. iScience. 26(10), 107780.
mla: Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal
Sex-Specific Stress Response after Injury and UCP2 Knockout.” IScience,
vol. 26, no. 10, 107780, Elsevier, 2023, doi:10.1016/j.isci.2023.107780.
short: M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino,
E.E. Pohl, S. Siegert, IScience 26 (2023).
date_created: 2023-09-24T22:01:11Z
date_published: 2023-10-20T00:00:00Z
date_updated: 2023-12-13T12:27:30Z
day: '20'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.isci.2023.107780
external_id:
isi:
- '001080403500001'
pmid:
- '37731609'
file:
- access_level: open_access
checksum: be1a560efdd96d20712311f4fc54aac2
content_type: application/pdf
creator: dernst
date_created: 2023-11-07T08:53:21Z
date_updated: 2023-11-07T08:53:21Z
file_id: '14497'
file_name: 2023_iScience_Maes.pdf
file_size: 8197935
relation: main_file
success: 1
file_date_updated: 2023-11-07T08:53:21Z
has_accepted_license: '1'
intvolume: ' 26'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: iScience
publication_identifier:
eissn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mitochondrial network adaptations of microglia reveal sex-specific stress response
after injury and UCP2 knockout
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '13126'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '11478'
abstract:
- lang: eng
text: Cerebral organoids differentiated from human-induced pluripotent stem cells
(hiPSC) provide a unique opportunity to investigate brain development. However,
organoids usually lack microglia, brain-resident immune cells, which are present
in the early embryonic brain and participate in neuronal circuit development.
Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3
and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol.
Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented,
3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When
we guide the retinal organoid differentiation with low-dosed BMP4, we prevent
cup development and enhance microglia and 3D-cysts formation. Mass spectrometry
identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed
this microglia-preferred environment also within the unguided protocol, providing
insight into microglial behavior and migration and offer a model to study how
they enter and distribute within the human brain.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank the scientific service units at ISTA, specifically the lab
support facility and imaging & optics facility for their support; Nicolas Armel
for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner
for their help in human brain tissue collection, Rouven Schulz for his insights
into the functional assays We thank all members of the Siegert group for constant
feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for
feedback on the manuscript. This project has received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung
Niederösterreich (grant No. Sc19-017 to V.H.).
article_number: '104580'
article_processing_charge: Yes
article_type: original
author:
- first_name: Katarina
full_name: Bartalska, Katarina
id: 4D883232-F248-11E8-B48F-1D18A9856A87
last_name: Bartalska
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of
microglia-like cell occurrence during retinal organoid differentiation. iScience.
2022;25(7). doi:10.1016/j.isci.2022.104580
apa: Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler,
K., … Siegert, S. (2022). A systematic characterization of microglia-like cell
occurrence during retinal organoid differentiation. IScience. Elsevier.
https://doi.org/10.1016/j.isci.2022.104580
chicago: Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro
Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization
of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience.
Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.
ieee: K. Bartalska et al., “A systematic characterization of microglia-like
cell occurrence during retinal organoid differentiation,” iScience, vol.
25, no. 7. Elsevier, 2022.
ista: Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech
T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence
during retinal organoid differentiation. iScience. 25(7), 104580.
mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like
Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol.
25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580.
short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler,
T. Czech, S. Siegert, IScience 25 (2022).
date_created: 2022-07-03T22:01:33Z
date_published: 2022-07-15T00:00:00Z
date_updated: 2023-11-02T12:21:33Z
day: '15'
ddc:
- '610'
department:
- _id: SaSi
doi: 10.1016/j.isci.2022.104580
ec_funded: 1
external_id:
isi:
- '000830428500005'
file:
- access_level: open_access
checksum: a470b74e1b3796c710189c81a4cd4329
content_type: application/pdf
creator: cchlebak
date_created: 2022-07-04T08:19:25Z
date_updated: 2022-07-04T08:19:25Z
file_id: '11480'
file_name: 2022_iScience_Bartalska.pdf
file_size: 19400048
relation: main_file
success: 1
file_date_updated: 2022-07-04T08:19:25Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: iScience
publication_identifier:
eissn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12117'
relation: other
status: public
scopus_import: '1'
status: public
title: A systematic characterization of microglia-like cell occurrence during retinal
organoid differentiation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 25
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor
Laboratory.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory,
doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2024-03-25T23:30:11Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11995'
abstract:
- lang: eng
text: G protein-coupled receptors (GPCRs) regulate processes ranging from immune
responses to neuronal signaling. However, ligands for many GPCRs remain unknown,
suffer from off-target effects or have poor bioavailability. Additionally, dissecting
cell type-specific responses is challenging when the same GPCR is expressed on
different cells within a tissue. Here, we overcome these limitations by engineering
DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest.
We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second
messenger and kinase activity, post-translational modifications, and protein-protein
interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation
in microglia, an immune cell capable of driving central nervous system inflammation.
When dissecting microglial inflammation, we included two additional DREADD-based
chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65
modulate the inflammatory response with high similarity to endogenous β2AR, while
DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation
of cell type-dependent pathways without known endogenous ligands.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: The authors thank the Scientific Service Units at ISTA, in particular
the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility,
and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco
Benevento for sharing reagents and expertise. This research was supported by a DOC
Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.
article_number: '4728'
article_processing_charge: No
article_type: original
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic
distinct signaling pathways and modulate microglia responses. Nature Communications.
2022;13. doi:10.1038/s41467-022-32390-1
apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022).
Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1
chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1.
ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature
Communications, vol. 13. Springer Nature, 2022.
ista: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs
mimic distinct signaling pathways and modulate microglia responses. Nature Communications.
13, 4728.
mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and
Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer
Nature, 2022, doi:10.1038/s41467-022-32390-1.
short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications
13 (2022).
date_created: 2022-08-28T22:01:59Z
date_published: 2022-08-15T00:00:00Z
date_updated: 2024-02-21T12:34:51Z
day: '15'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-022-32390-1
external_id:
isi:
- '000840984400032'
pmid:
- '35970889'
file:
- access_level: open_access
checksum: 191d9db0266e14a28d3a56dc7f65da84
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-29T06:44:30Z
date_updated: 2022-08-29T06:44:30Z
file_id: '12002'
file_name: 2022_NatComm_Schulz.pdf
file_size: 7317396
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success: 1
file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
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month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/dreaddful-mimicry/
record:
- id: '11945'
relation: part_of_dissertation
status: public
- id: '11542'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12117'
abstract:
- lang: eng
text: "To understand how potential gene manipulations affect in vitro microglia,
we provide a set of short protocols to evaluate microglia identity and function.
We detail steps for immunostaining to determine microglia identity. We describe
three functional assays for microglia: phagocytosis, calcium response following
ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these
protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but
they can be also applied to other in vitro microglial models including primary
mouse microglia.\r\nFor complete details on the use and execution of this protocol,
please refer to Bartalska et al. (2022).1"
acknowledged_ssus:
- _id: Bio
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich
(grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for
their insights into functional assays and data analysis, Verena Seiboth for insights
into necessary institutional permission, and ISTA imaging & optics facility (IOF)
especially Bernhard Hochreiter for their support.
article_number: '101866'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity
and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866
apa: Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived
microglia identity and function by immunostaining, phagocytosis, calcium activity,
and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866
chicago: Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human
IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis,
Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022.
https://doi.org/10.1016/j.xpro.2022.101866.
ieee: V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022.
ista: Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 3(4), 101866.
mla: Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity
and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation
Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866.
short: V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).
date_created: 2023-01-12T11:56:38Z
date_published: 2022-12-16T00:00:00Z
date_updated: 2023-11-02T12:21:32Z
day: '16'
ddc:
- '570'
department:
- _id: SaSi
- _id: GradSch
doi: 10.1016/j.xpro.2022.101866
ec_funded: 1
file:
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checksum: 3c71b8a60633d42c2f77c49025d5559b
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T09:50:51Z
date_updated: 2023-01-23T09:50:51Z
file_id: '12340'
file_name: 2022_STARProtocols_Huebschmann.pdf
file_size: 6251945
relation: main_file
success: 1
file_date_updated: 2023-01-23T09:50:51Z
has_accepted_license: '1'
intvolume: ' 3'
issue: '4'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '11478'
relation: other
status: public
scopus_import: '1'
status: public
title: Assessing human iPSC-derived microglia identity and function by immunostaining,
phagocytosis, calcium activity, and inflammation assay
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 3
year: '2022'
...
---
_id: '12244'
abstract:
- lang: eng
text: Environmental cues influence the highly dynamic morphology of microglia. Strategies
to characterize these changes usually involve user-selected morphometric features,
which preclude the identification of a spectrum of context-dependent morphological
phenotypes. Here we develop MorphOMICs, a topological data analysis approach,
which enables semiautomatic mapping of microglial morphology into an atlas of
cue-dependent phenotypes and overcomes feature-selection biases and biological
variability. We extract spatially heterogeneous and sexually dimorphic morphological
phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines
with maturation but increases over the disease trajectories in two neurodegeneration
mouse models, with females showing a faster morphological shift in affected brain
regions. Remarkably, microglia morphologies reflect an adaptation upon repeated
exposure to ketamine anesthesia and do not recover to control morphologies. Finally,
we demonstrate that both long primary processes and short terminal processes provide
distinct insights to morphological phenotypes. MorphOMICs opens a new perspective
to characterize microglial morphology.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
acknowledgement: We thank the scientific service units at ISTA, in particular M. Schunn’s
team at the preclinical facility, and especially our colony manager S. Haslinger,
for excellent support. We are also grateful to the ISTA Imaging & Optics Facility,
and in particular C. Sommer for helping with the data file conversions. We thank
R. Erhart from the ISTA Scientific Computing Unit for improving the script performance.
We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert
group for constant feedback on the project and on the manuscript. This research
was supported by the European Union Horizon 2020 research and innovation program
under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the
European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding
to the Blue Brain Project, a research center of the École polytechnique fédérale
de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes
of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB
Foundation. The funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Lida
full_name: Kanari, Lida
last_name: Kanari
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Martina
full_name: Scolamiero, Martina
last_name: Scolamiero
- first_name: Jens
full_name: Agerberg, Jens
last_name: Agerberg
- first_name: Hansruedi
full_name: Mathys, Hansruedi
last_name: Mathys
- first_name: Li-Huei
full_name: Tsai, Li-Huei
last_name: Tsai
- first_name: Wojciech
full_name: Chachólski, Wojciech
last_name: Chachólski
- first_name: Kathryn
full_name: Hess, Kathryn
last_name: Hess
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology,
morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
2022;25(10):1379-1393. doi:10.1038/s41593-022-01167-6
apa: Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero,
M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
Springer Nature. https://doi.org/10.1038/s41593-022-01167-6
chicago: Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven
Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial
Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature
Neuroscience. Springer Nature, 2022. https://doi.org/10.1038/s41593-022-01167-6.
ieee: G. Colombo et al., “A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes,” Nature Neuroscience,
vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.
ista: Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg
J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping
microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.
Nature Neuroscience. 25(10), 1379–1393.
mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs,
Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature Neuroscience,
vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:10.1038/s41593-022-01167-6.
short: G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero,
J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature
Neuroscience 25 (2022) 1379–1393.
date_created: 2023-01-16T09:53:07Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2024-03-25T23:30:10Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41593-022-01167-6
ec_funded: 1
external_id:
isi:
- '000862214700001'
pmid:
- '36180790'
file:
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checksum: 28431146873096f52e0107b534f178c9
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T08:06:56Z
date_updated: 2023-01-30T08:06:56Z
file_id: '12437'
file_name: 2022_NatureNeuroscience_Colombo.pdf
file_size: 23789835
relation: main_file
success: 1
file_date_updated: 2023-01-30T08:06:56Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '10'
keyword:
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1379-1393
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/
record:
- id: '12378'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region
and sex-dependent phenotypes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 25
year: '2022'
...
---
_id: '9642'
abstract:
- lang: eng
text: Perineuronal nets (PNNs), components of the extracellular matrix, preferentially
coat parvalbumin-positive interneurons and constrain critical-period plasticity
in the adult cerebral cortex. Current strategies to remove PNN are long-lasting,
invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic
ketamine as a method with minimal behavioral effect. We find that this paradigm
strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like
plasticity. Microglia are critically involved in PNN loss because they engage
with parvalbumin-positive neurons in their defined cortical layer. We identify
external 60-Hz light-flickering entrainment to recapitulate microglia-mediated
PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques,
does not induce PNN loss, suggesting microglia might functionally tune to distinct
brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative
form of PNN intervention in the healthy adult brain.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank the scientific service units at IST Austria, especially
the IST bioimaging facility, the preclinical facility, and, specifically, Michael
Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the
Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for
the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King,
and all Siegert group members for constant feedback on the project and manuscript;
Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination
for OD plasticity experiments; and Ana Morello from MIT for technical assistance
with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian
Academy of Sciences at the Institute of Science and Technology Austria to R.S.,
from the European Union Horizon 2020 research and innovation program under the Marie
Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the
European Research Council (grant 715571 to S.S.), and the National Eye Institute
of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.)
and R01EY023037 (diversity supplement to H.D.J-C.).
article_number: '109313'
article_processing_charge: No
article_type: original
author:
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Héctor
full_name: De Jesús-Cortés, Héctor
last_name: De Jesús-Cortés
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Balint
full_name: Nagy, Balint
id: 93C65ECC-A6F2-11E9-8DF9-9712E6697425
last_name: Nagy
- first_name: Francis
full_name: Reilly-Andújar, Francis
last_name: Reilly-Andújar
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Mark F.
full_name: Bear, Mark F.
last_name: Bear
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal
nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment
in the healthy brain. Cell Reports. 2021;36(1). doi:10.1016/j.celrep.2021.109313
apa: Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar,
F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly
upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109313
chicago: Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret
E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia
Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure
or 60-Hz Light Entrainment in the Healthy Brain.” Cell Reports. Elsevier,
2021. https://doi.org/10.1016/j.celrep.2021.109313.
ieee: A. Venturino et al., “Microglia enable mature perineuronal nets disassembly
upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,”
Cell Reports, vol. 36, no. 1. Elsevier, 2021.
ista: Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar
F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia
enable mature perineuronal nets disassembly upon anesthetic ketamine exposure
or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.
mla: Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly
upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.”
Cell Reports, vol. 36, no. 1, 109313, Elsevier, 2021, doi:10.1016/j.celrep.2021.109313.
short: A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar,
G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports
36 (2021).
date_created: 2021-07-11T22:01:16Z
date_published: 2021-07-06T00:00:00Z
date_updated: 2023-08-10T14:09:39Z
day: '06'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.celrep.2021.109313
ec_funded: 1
external_id:
isi:
- '000670188500004'
pmid:
- '34233180'
file:
- access_level: open_access
checksum: f056255f6d01fd9a86b5387635928173
content_type: application/pdf
creator: cziletti
date_created: 2021-07-19T13:32:17Z
date_updated: 2021-07-19T13:32:17Z
file_id: '9693'
file_name: 2021_CellReports_Venturino.pdf
file_size: 56388540
relation: main_file
success: 1
file_date_updated: 2021-07-19T13:32:17Z
has_accepted_license: '1'
intvolume: ' 36'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/the-twinkle-and-the-brain/
scopus_import: '1'
status: public
title: Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine
exposure or 60-Hz light entrainment in the healthy brain
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 36
year: '2021'
...
---
_id: '10565'
abstract:
- lang: eng
text: 'Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates
juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal
nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally
and it degrades the ECM for several weeks. Here, we provide two minimally invasive
and transient protocols for microglia-enabled PNN disassembly in mouse cortex:
repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz
light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes.
For complete details on the use and execution of this protocol, please refer to
Venturino et al. (2021).'
acknowledged_ssus:
- _id: Bio
acknowledgement: This research was supported by the European Research Council (grant
715571 to S.S.). We thank Rouven Schulz, Michael Schunn, Claudia Gold, Gabriel Krens,
Sarah Gorkiewicz, Margaret Maes, Jürgen Siegert, Marco Benevento, and Sara Oakeley
for comments on the manuscript and the IST Austria Bioimaging Facility for the technical
support.
article_number: '101012'
article_processing_charge: Yes
article_type: original
author:
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Venturino A, Siegert S. Minimally invasive protocols and quantification for
microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
2021;2(4). doi:10.1016/j.xpro.2021.101012
apa: Venturino, A., & Siegert, S. (2021). Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
Elsevier ; Cell Press. https://doi.org/10.1016/j.xpro.2021.101012
chicago: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols
and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse
Brain.” STAR Protocols. Elsevier ; Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.101012.
ieee: A. Venturino and S. Siegert, “Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain,” STAR Protocols,
vol. 2, no. 4. Elsevier ; Cell Press, 2021.
ista: Venturino A, Siegert S. 2021. Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
2(4), 101012.
mla: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and
Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.”
STAR Protocols, vol. 2, no. 4, 101012, Elsevier ; Cell Press, 2021, doi:10.1016/j.xpro.2021.101012.
short: A. Venturino, S. Siegert, STAR Protocols 2 (2021).
date_created: 2021-12-19T23:01:32Z
date_published: 2021-12-17T00:00:00Z
date_updated: 2023-11-16T13:11:04Z
day: '17'
ddc:
- '573'
department:
- _id: SaSi
doi: 10.1016/j.xpro.2021.101012
ec_funded: 1
file:
- access_level: open_access
checksum: 9ea2501056c5df99e84726b845e9b976
content_type: application/pdf
creator: cchlebak
date_created: 2021-12-20T08:58:40Z
date_updated: 2021-12-20T08:58:40Z
file_id: '10570'
file_name: 2021_STARProt_Venturino.pdf
file_size: 6207060
relation: main_file
success: 1
file_date_updated: 2021-12-20T08:58:40Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Elsevier ; Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Minimally invasive protocols and quantification for microglia-mediated perineuronal
net disassembly in mouse brain
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2023-11-16T13:12:03Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...
---
_id: '6521'
abstract:
- lang: eng
text: Microglia have emerged as a critical component of neurodegenerative diseases.
Genetic manipulation of microglia can elucidate their functional impact in disease.
In neuroscience, recombinant viruses such as lentiviruses and adeno-associated
viruses (AAVs) have been successfully used to target various cell types in the
brain, although effective transduction of microglia is rare. In this review, we
provide a short background of lentiviruses and AAVs, and strategies for designing
recombinant viral vectors. Then, we will summarize recent literature on successful
microglial transductions in vitro and in vivo, and discuss the current challenges.
Finally, we provide guidelines for reporting the efficiency and specificity of
viral targeting in microglia, which will enable the microglial research community
to assess and improve methodologies for future studies.
article_number: '134310'
article_processing_charge: No
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: 'Maes ME, Colombo G, Schulz R, Siegert S. Targeting microglia with lentivirus
and AAV: Recent advances and remaining challenges. Neuroscience Letters.
2019;707. doi:10.1016/j.neulet.2019.134310'
apa: 'Maes, M. E., Colombo, G., Schulz, R., & Siegert, S. (2019). Targeting
microglia with lentivirus and AAV: Recent advances and remaining challenges. Neuroscience
Letters. Elsevier. https://doi.org/10.1016/j.neulet.2019.134310'
chicago: 'Maes, Margaret E, Gloria Colombo, Rouven Schulz, and Sandra Siegert. “Targeting
Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.”
Neuroscience Letters. Elsevier, 2019. https://doi.org/10.1016/j.neulet.2019.134310.'
ieee: 'M. E. Maes, G. Colombo, R. Schulz, and S. Siegert, “Targeting microglia with
lentivirus and AAV: Recent advances and remaining challenges,” Neuroscience
Letters, vol. 707. Elsevier, 2019.'
ista: 'Maes ME, Colombo G, Schulz R, Siegert S. 2019. Targeting microglia with lentivirus
and AAV: Recent advances and remaining challenges. Neuroscience Letters. 707,
134310.'
mla: 'Maes, Margaret E., et al. “Targeting Microglia with Lentivirus and AAV: Recent
Advances and Remaining Challenges.” Neuroscience Letters, vol. 707, 134310,
Elsevier, 2019, doi:10.1016/j.neulet.2019.134310.'
short: M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019).
date_created: 2019-06-05T13:16:24Z
date_published: 2019-08-10T00:00:00Z
date_updated: 2023-08-28T09:30:57Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.neulet.2019.134310
ec_funded: 1
external_id:
isi:
- '000486094600037'
pmid:
- '31158432'
file:
- access_level: open_access
checksum: 553c9dbd39727fbed55ee991c51ca4d1
content_type: application/pdf
creator: dernst
date_created: 2019-06-08T11:44:20Z
date_updated: 2020-07-14T12:47:33Z
file_id: '6551'
file_name: 2019_Neuroscience_Maes.pdf
file_size: 1779287
relation: main_file
file_date_updated: 2020-07-14T12:47:33Z
has_accepted_license: '1'
intvolume: ' 707'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Neuroscience Letters
publication_identifier:
issn:
- 0304-3940
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Targeting microglia with lentivirus and AAV: Recent advances and remaining
challenges'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 707
year: '2019'
...
---
_id: '1613'
abstract:
- lang: eng
text: "In the last decade, induced pluripotent stem (iPS) cells have revolutionized
the utility of human in vitro models of neurological disease. The iPS-derived
and differentiated cells allow researchers to study the impact of a distinct cell
type in health and disease as well as performing therapeutic drug screens on a
human genetic background. In particular, clinical trials for Alzheimer's disease
(AD) have been often failing. Two of the potential reasons are first, the species
gap involved in proceeding from initial discoveries in rodent models to human
studies, and second, an unsatisfying patient stratification, meaning subgrouping
patients based on the disease severity due to the lack of phenotypic and genetic
markers. iPS cells overcome this obstacles and will improve our understanding
of disease subtypes in AD. They allow researchers conducting in depth characterization
of neural cells from both familial and sporadic AD patients as well as preclinical
screens on human cells.\r\n\r\nIn this review, we briefly outline the status quo
of iPS cell research in neurological diseases along with the general advantages
and pitfalls of these models. We summarize how genome-editing techniques such
as CRISPR/Cas will allow researchers to reduce the problem of genomic variability
inherent to human studies, followed by recent iPS cell studies relevant to AD.
We then focus on current techniques for the differentiation of iPS cells into
neural cell types that are relevant to AD research. Finally, we discuss how the
generation of three-dimensional cell culture systems will be important for understanding
AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional
iPS cell models can provide platforms for drug discovery and translational studies
into the treatment of AD."
acknowledgement: This work was supported by NIH grant R01-AG047661 to LHT. The art
in Fig. 1 was created by Julian Wong.
author:
- first_name: Alison
full_name: Mungenast, Alison
last_name: Mungenast
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Li
full_name: Tsai, Li
last_name: Tsai
citation:
ama: Mungenast A, Siegert S, Tsai L. Modeling Alzheimer’s disease with human induced
pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 2016;73:13-31.
doi:doi:10.1016/j.mcn.2015.11.010
apa: Mungenast, A., Siegert, S., & Tsai, L. (2016). Modeling Alzheimer’s disease
with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience.
Academic Press. https://doi.org/doi:10.1016/j.mcn.2015.11.010
chicago: Mungenast, Alison, Sandra Siegert, and Li Tsai. “Modeling Alzheimer’s Disease
with Human Induced Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience.
Academic Press, 2016. https://doi.org/doi:10.1016/j.mcn.2015.11.010.
ieee: A. Mungenast, S. Siegert, and L. Tsai, “Modeling Alzheimer’s disease with
human induced pluripotent stem (iPS) cells,” Molecular and Cellular Neuroscience,
vol. 73. Academic Press, pp. 13–31, 2016.
ista: Mungenast A, Siegert S, Tsai L. 2016. Modeling Alzheimer’s disease with human
induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 73,
13–31.
mla: Mungenast, Alison, et al. “Modeling Alzheimer’s Disease with Human Induced
Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience, vol.
73, Academic Press, 2016, pp. 13–31, doi:doi:10.1016/j.mcn.2015.11.010.
short: A. Mungenast, S. Siegert, L. Tsai, Molecular and Cellular Neuroscience 73
(2016) 13–31.
date_created: 2018-12-11T11:53:02Z
date_published: 2016-06-01T00:00:00Z
date_updated: 2021-01-12T06:52:00Z
day: '01'
ddc:
- '616'
doi: doi:10.1016/j.mcn.2015.11.010
extern: '1'
file:
- access_level: open_access
checksum: 620254114e04d5d6e7f37d15e4b8ace4
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:50Z
date_updated: 2020-07-14T12:45:07Z
file_id: '4970'
file_name: IST-2018-979-v1+1_Mungenast_2015_acceptedManuscript.pdf
file_size: 632915
relation: main_file
file_date_updated: 2020-07-14T12:45:07Z
has_accepted_license: '1'
intvolume: ' 73'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Submitted Version
page: 13 - 31
publication: Molecular and Cellular Neuroscience
publication_status: published
publisher: Academic Press
publist_id: '5553'
pubrep_id: '979'
quality_controlled: '1'
status: public
title: Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 73
year: '2016'
...
---
_id: '1253'
abstract:
- lang: eng
text: This article provides an introduction to the role of microRNAs in the nervous
system and outlines their potential involvement in the pathophysiology of schizophrenia,
which is hypothesized to arise owing to environmental factors and genetic predisposition.
article_processing_charge: No
author:
- first_name: Lihuei
full_name: Tsai, Lihuei
last_name: Tsai
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Tsai L, Siegert S. How MicroRNAs Are involved in splitting the mind. JAMA
Psychiatry. 2016;73(4):409-410. doi:10.1001/jamapsychiatry.2015.3144
apa: Tsai, L., & Siegert, S. (2016). How MicroRNAs Are involved in splitting
the mind. JAMA Psychiatry. American Medical Association. https://doi.org/10.1001/jamapsychiatry.2015.3144
chicago: Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting
the Mind.” JAMA Psychiatry. American Medical Association, 2016. https://doi.org/10.1001/jamapsychiatry.2015.3144.
ieee: L. Tsai and S. Siegert, “How MicroRNAs Are involved in splitting the mind,”
JAMA Psychiatry, vol. 73, no. 4. American Medical Association, pp. 409–410,
2016.
ista: Tsai L, Siegert S. 2016. How MicroRNAs Are involved in splitting the mind.
JAMA Psychiatry. 73(4), 409–410.
mla: Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting
the Mind.” JAMA Psychiatry, vol. 73, no. 4, American Medical Association,
2016, pp. 409–10, doi:10.1001/jamapsychiatry.2015.3144.
short: L. Tsai, S. Siegert, JAMA Psychiatry 73 (2016) 409–410.
date_created: 2018-12-11T11:50:58Z
date_published: 2016-04-01T00:00:00Z
date_updated: 2024-02-14T12:07:22Z
day: '01'
ddc:
- '576'
- '610'
department:
- _id: SaSi
doi: 10.1001/jamapsychiatry.2015.3144
external_id:
pmid:
- '26963490'
file:
- access_level: open_access
checksum: 649aee381f30f7ef7e9efa912d41c2e3
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:24Z
date_updated: 2020-07-14T12:44:41Z
file_id: '5278'
file_name: IST-2018-981-v1+1_YNP150011_annotatedproof_FINAL.pdf
file_size: 601679
relation: main_file
file_date_updated: 2020-07-14T12:44:41Z
has_accepted_license: '1'
intvolume: ' 73'
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 409 - 410
pmid: 1
publication: JAMA Psychiatry
publication_identifier:
issn:
- 2168-622X
publication_status: published
publisher: American Medical Association
publist_id: '6074'
pubrep_id: '981'
quality_controlled: '1'
scopus_import: '1'
status: public
title: How MicroRNAs Are involved in splitting the mind
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 73
year: '2016'
...
---
_id: '1802'
abstract:
- lang: eng
text: Noncoding variants in the human MIR137 gene locus increase schizophrenia risk
with genome-wide significance. However, the functional consequence of these risk
alleles is unknown. Here we examined induced human neurons harboring the minor
alleles of four disease-associated single nucleotide polymorphisms in MIR137.
We observed increased MIR137 levels compared to those in major allele–carrying
cells. microRNA-137 gain of function caused downregulation of the presynaptic
target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired
vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic
vesicle pool distribution, impaired induction of mossy fiber long-term potentiation
and deficits in hippocampus-dependent learning and memory. By sequestering endogenous
miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement
of Syt1 expression partially restored synaptic plasticity, demonstrating the importance
of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by
which miR-137 dysregulation can impair synaptic plasticity in the hippocampus.
acknowledgement: S.S. was supported by a Human Frontier Science Program (HFSP) long-term
postdoctoral fellowship and a Swiss National Science Foundation fellowship for prospective
researchers. E.J.K. was supported by a Simons Foundation Postdoctoral Fellowship.
A.R. was supported by a NARSAD Young Investigator Award. This work was supported
by a Seed Grant from the Simons Center for the Social Brain and US National Institutes
of Health grant RO1 MH 091115 to L.-H.T.
author:
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Jinsoo
full_name: Seo, Jinsoo
last_name: Seo
- first_name: Ester
full_name: Kwon, Ester J
last_name: Kwon
- first_name: Andrii
full_name: Rudenko, Andrii
last_name: Rudenko
- first_name: Sukhee
full_name: Cho, Sukhee
last_name: Cho
- first_name: Wenyuan
full_name: Wang, Wenyuan
last_name: Wang
- first_name: Zachary
full_name: Flood, Zachary C
last_name: Flood
- first_name: Anthony
full_name: Martorell, Anthony J
last_name: Martorell
- first_name: Maria
full_name: Ericsson, Maria
last_name: Ericsson
- first_name: Alison
full_name: Mungenast, Alison E
last_name: Mungenast
- first_name: Lihuei
full_name: Tsai, Lihuei
last_name: Tsai
citation:
ama: Siegert S, Seo J, Kwon E, et al. The schizophrenia risk gene product miR-137
alters presynaptic plasticity. Nature Neuroscience. 2015;18:1008-1016.
doi:10.1038/nn.4023
apa: Siegert, S., Seo, J., Kwon, E., Rudenko, A., Cho, S., Wang, W., … Tsai, L.
(2015). The schizophrenia risk gene product miR-137 alters presynaptic plasticity.
Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.4023
chicago: Siegert, Sandra, Jinsoo Seo, Ester Kwon, Andrii Rudenko, Sukhee Cho, Wenyuan
Wang, Zachary Flood, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters
Presynaptic Plasticity.” Nature Neuroscience. Nature Publishing Group,
2015. https://doi.org/10.1038/nn.4023.
ieee: S. Siegert et al., “The schizophrenia risk gene product miR-137 alters
presynaptic plasticity,” Nature Neuroscience, vol. 18. Nature Publishing
Group, pp. 1008–1016, 2015.
ista: Siegert S, Seo J, Kwon E, Rudenko A, Cho S, Wang W, Flood Z, Martorell A,
Ericsson M, Mungenast A, Tsai L. 2015. The schizophrenia risk gene product miR-137
alters presynaptic plasticity. Nature Neuroscience. 18, 1008–1016.
mla: Siegert, Sandra, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters
Presynaptic Plasticity.” Nature Neuroscience, vol. 18, Nature Publishing
Group, 2015, pp. 1008–16, doi:10.1038/nn.4023.
short: S. Siegert, J. Seo, E. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, A. Martorell,
M. Ericsson, A. Mungenast, L. Tsai, Nature Neuroscience 18 (2015) 1008–1016.
date_created: 2018-12-11T11:54:05Z
date_published: 2015-07-01T00:00:00Z
date_updated: 2021-01-12T06:53:18Z
day: '01'
doi: 10.1038/nn.4023
extern: 1
intvolume: ' 18'
month: '07'
page: 1008 - 1016
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '5308'
quality_controlled: 0
status: public
title: The schizophrenia risk gene product miR-137 alters presynaptic plasticity
type: journal_article
volume: 18
year: '2015'
...
---
_id: '1803'
abstract:
- lang: eng
text: Repeated stress has been suggested to underlie learning and memory deficits
via the basolateral amygdala (BLA) and the hippocampus; however, the functional
contribution of BLA inputs to the hippocampus and their molecular repercussions
are not well understood. Here we show that repeated stress is accompanied by generation
of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation
of glucocorticoid receptors, increased HDAC2 expression, and reduced expression
of memoryrelated genes in the hippocampus. A combination of optogenetic and pharmacosynthetic
approaches shows that BLA activation is both necessary and sufficient for stress-associated
molecular changes and memory impairments. Furthermore, we show that this effect
relies on direct glutamatergic projections from the BLA to the dorsal hippocampus.
Finally, we show that p25 generation is necessary for the stress-induced memory
dysfunction. Taken together, our data provide a neural circuit model for stress-induced
hippocampal memory deficits through BLA activity-dependent p25 generation.
acknowledgement: |-
AG047661; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung
NS051874; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung
SNSF; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung
author:
- first_name: Damien
full_name: Rei, Damien
last_name: Rei
- first_name: Xenos
full_name: Mason, Xenos
last_name: Mason
- first_name: Jinsoo
full_name: Seo, Jinsoo
last_name: Seo
- first_name: Johannes
full_name: Gräff, Johannes
last_name: Gräff
- first_name: Andrii
full_name: Rudenko, Andrii
last_name: Rudenko
- first_name: Jùn
full_name: Wang, Jùn
last_name: Wang
- first_name: Richard
full_name: Rueda, Richard
last_name: Rueda
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Sukhee
full_name: Cho, Sukhee
last_name: Cho
- first_name: Rebecca
full_name: Canter, Rebecca G
last_name: Canter
- first_name: Alison
full_name: Mungenast, Alison E
last_name: Mungenast
- first_name: Karl
full_name: Deisseroth, Karl A
last_name: Deisseroth
- first_name: Lihuei
full_name: Tsai, Lihuei
last_name: Tsai
citation:
ama: Rei D, Mason X, Seo J, et al. Basolateral amygdala bidirectionally modulates
stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent
pathway. PNAS. 2015;112(23):7291-7296. doi:10.1073/pnas.1415845112
apa: Rei, D., Mason, X., Seo, J., Gräff, J., Rudenko, A., Wang, J., … Tsai, L. (2015).
Basolateral amygdala bidirectionally modulates stress induced hippocampal learning
and memory deficits through a p25/Cdk5-dependent pathway. PNAS. National
Academy of Sciences. https://doi.org/10.1073/pnas.1415845112
chicago: Rei, Damien, Xenos Mason, Jinsoo Seo, Johannes Gräff, Andrii Rudenko, Jùn
Wang, Richard Rueda, et al. “Basolateral Amygdala Bidirectionally Modulates Stress
Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent
Pathway.” PNAS. National Academy of Sciences, 2015. https://doi.org/10.1073/pnas.1415845112.
ieee: D. Rei et al., “Basolateral amygdala bidirectionally modulates stress
induced hippocampal learning and memory deficits through a p25/Cdk5-dependent
pathway,” PNAS, vol. 112, no. 23. National Academy of Sciences, pp. 7291–7296,
2015.
ista: Rei D, Mason X, Seo J, Gräff J, Rudenko A, Wang J, Rueda R, Siegert S, Cho
S, Canter R, Mungenast A, Deisseroth K, Tsai L. 2015. Basolateral amygdala bidirectionally
modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent
pathway. PNAS. 112(23), 7291–7296.
mla: Rei, Damien, et al. “Basolateral Amygdala Bidirectionally Modulates Stress
Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent
Pathway.” PNAS, vol. 112, no. 23, National Academy of Sciences, 2015, pp.
7291–96, doi:10.1073/pnas.1415845112.
short: D. Rei, X. Mason, J. Seo, J. Gräff, A. Rudenko, J. Wang, R. Rueda, S. Siegert,
S. Cho, R. Canter, A. Mungenast, K. Deisseroth, L. Tsai, PNAS 112 (2015) 7291–7296.
date_created: 2018-12-11T11:54:06Z
date_published: 2015-06-09T00:00:00Z
date_updated: 2021-01-12T06:53:18Z
day: '09'
doi: 10.1073/pnas.1415845112
extern: 1
intvolume: ' 112'
issue: '23'
month: '06'
page: 7291 - 7296
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '5307'
quality_controlled: 0
status: public
title: Basolateral amygdala bidirectionally modulates stress induced hippocampal learning
and memory deficits through a p25/Cdk5-dependent pathway
type: journal_article
volume: 112
year: '2015'
...
---
_id: '1801'
abstract:
- lang: eng
text: Brain circuits are assembled from a large variety of morphologically and functionally
diverse cell types. It is not known how the intermingled cell types of an individual
adult brain region differ in their expressed genomes. Here we describe an atlas
of cell type transcriptomes in one brain region, the mouse retina. We found that
each adult cell type expressed a specific set of genes, including a unique set
of transcription factors, forming a 'barcode' for cell identity. Cell type transcriptomes
carried enough information to categorize cells into morphological classes and
types. Several genes that were specifically expressed in particular retinal circuit
elements, such as inhibitory neuron types, are associated with eye diseases. The
resource described here allows gene expression to be compared across adult retinal
cell types, experimenting with specific transcription factors to differentiate
stem or somatic cells to retinal cell types, and predicting cellular targets of
newly discovered disease-associated genes.
acknowledgement: The study was supported by Friedrich Miescher Institute funds, Alcon
award, a National Center of Competence in Research Genetics grant, a European Research
Council grant, a Swiss-Hungarian grant, and RETICIRC, TREATRUSH, SEEBETTER and OPTONEURO
grants from the European Union to B.R.
author:
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Erik
full_name: Cabuy, Erik
last_name: Cabuy
- first_name: Brigitte
full_name: Scherf, Brigitte G
last_name: Scherf
- first_name: Hubertus
full_name: Kohler, Hubertus
last_name: Kohler
- first_name: Satchidananda
full_name: Panda, Satchidananda
last_name: Panda
- first_name: Yunzheng
full_name: Le, Yunzheng
last_name: Le
- first_name: Hans
full_name: Fehling, Hans J
last_name: Fehling
- first_name: Dimos
full_name: Gaidatzis, Dimos
last_name: Gaidatzis
- first_name: Michael
full_name: Stadler, Michael B
last_name: Stadler
- first_name: Botond
full_name: Roska, Botond M
last_name: Roska
citation:
ama: Siegert S, Cabuy E, Scherf B, et al. Transcriptional code and disease map for
adult retinal cell types. Nature Neuroscience. 2012;15(3):487-495. doi:10.1038/nn.3032
apa: Siegert, S., Cabuy, E., Scherf, B., Kohler, H., Panda, S., Le, Y., … Roska,
B. (2012). Transcriptional code and disease map for adult retinal cell types.
Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.3032
chicago: Siegert, Sandra, Erik Cabuy, Brigitte Scherf, Hubertus Kohler, Satchidananda
Panda, Yunzheng Le, Hans Fehling, Dimos Gaidatzis, Michael Stadler, and Botond
Roska. “Transcriptional Code and Disease Map for Adult Retinal Cell Types.” Nature
Neuroscience. Nature Publishing Group, 2012. https://doi.org/10.1038/nn.3032.
ieee: S. Siegert et al., “Transcriptional code and disease map for adult
retinal cell types,” Nature Neuroscience, vol. 15, no. 3. Nature Publishing
Group, pp. 487–495, 2012.
ista: Siegert S, Cabuy E, Scherf B, Kohler H, Panda S, Le Y, Fehling H, Gaidatzis
D, Stadler M, Roska B. 2012. Transcriptional code and disease map for adult retinal
cell types. Nature Neuroscience. 15(3), 487–495.
mla: Siegert, Sandra, et al. “Transcriptional Code and Disease Map for Adult Retinal
Cell Types.” Nature Neuroscience, vol. 15, no. 3, Nature Publishing Group,
2012, pp. 487–95, doi:10.1038/nn.3032.
short: S. Siegert, E. Cabuy, B. Scherf, H. Kohler, S. Panda, Y. Le, H. Fehling,
D. Gaidatzis, M. Stadler, B. Roska, Nature Neuroscience 15 (2012) 487–495.
date_created: 2018-12-11T11:54:05Z
date_published: 2012-03-01T00:00:00Z
date_updated: 2021-01-12T06:53:17Z
day: '01'
doi: 10.1038/nn.3032
extern: 1
intvolume: ' 15'
issue: '3'
month: '03'
page: 487 - 495
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '5309'
quality_controlled: 0
status: public
title: Transcriptional code and disease map for adult retinal cell types
type: journal_article
volume: 15
year: '2012'
...
---
_id: '1800'
abstract:
- lang: eng
text: Retinitis pigmentosa refers to a diverse group of hereditary diseases that
lead to incurable blindness, affecting two million people worldwide. As a common
pathology, rod photoreceptors die early, whereas light-insensitive, morphologically
altered cone photoreceptors persist longer. It is unknown if these cones are accessible
for therapeutic intervention. Here, we show that expression of archaebacterial
halorhodopsin in light-insensitive cones can substitute for the native phototransduction
cascade and restore light sensitivity in mouse models of retinitis pigmentosa.
Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated
retinal circuit functions (including directional selectivity), activate cortical
circuits, and mediate visually guided behaviors. Using human ex vivo retinas,
we show that halorhodopsin can reactivate light-insensitive human photoreceptors.
Finally, we identified blind patients with persisting, light-insensitive cones
for potential halorhodopsin-based therapy.
acknowledgement: This study was supported by Friedrich Miescher Institute funds; a
U.S. Office of Naval Research Naval International Cooperative Opportunities in Science
and Technology Program grant; a Marie Curie Excellence grant and a European Union
(EU) HEALTH-F2-223156 grant to B.R.; a grant from the EU (RETICIRC) to B.R. and
S.P.; grants from the Agence nationale de la recherche (MEDINAS, RETINE) to S.P.;
a Center Grant from Foundation Fighting Blindness (U.S.) to S.M.-S. and J.A.S.;
grants from the Swiss National Science Foundation and the EU to D.T.; a grant from
the EU (TREATRUSH) to J.A.S., S.P., and B.R.; a Marie Curie Postdoctoral Fellowship
to D.B.; and a National Centers of Competence in Research Frontiers in Genetics
fellowship to V.B. and A.C.G. The Ocular Genetics Unit at Trinity College Dublin
is supported by Science Foundation Ireland
author:
- first_name: Volker
full_name: Busskamp, Volker
last_name: Busskamp
- first_name: Jens
full_name: Duebel, Jens
last_name: Duebel
- first_name: Dávid
full_name: Bálya, Dávid
last_name: Bálya
- first_name: Mathias
full_name: Fradot, Mathias
last_name: Fradot
- first_name: Tim
full_name: Viney, Tim J
last_name: Viney
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Anna
full_name: Groner, Anna C
last_name: Groner
- first_name: Erik
full_name: Cabuy, Erik
last_name: Cabuy
- first_name: Valérie
full_name: Forster, Valérie
last_name: Forster
- first_name: Mathias
full_name: Seeliger, Mathias W
last_name: Seeliger
- first_name: Martin
full_name: Biel, Martin
last_name: Biel
- first_name: Peter
full_name: Humphries, Peter
last_name: Humphries
- first_name: Michel
full_name: Pâques, Michel
last_name: Pâques
- first_name: Saddek
full_name: Mohand-Saïd, Saddek
last_name: Mohand Saïd
- first_name: Didier
full_name: Trono, Didier
last_name: Trono
- first_name: Karl
full_name: Deisseroth, Karl A
last_name: Deisseroth
- first_name: José
full_name: Sähel, José A
last_name: Sähel
- first_name: Serge
full_name: Picaud, Serge A
last_name: Picaud
- first_name: Botond
full_name: Roska, Botond M
last_name: Roska
citation:
ama: Busskamp V, Duebel J, Bálya D, et al. Genetic reactivation of cone photoreceptors
restores visual responses in retinitis pigmentosa. Science. 2010;329(5990):413-417.
doi:10.1126/science.1190897
apa: Busskamp, V., Duebel, J., Bálya, D., Fradot, M., Viney, T., Siegert, S., …
Roska, B. (2010). Genetic reactivation of cone photoreceptors restores visual
responses in retinitis pigmentosa. Science. American Association for the
Advancement of Science. https://doi.org/10.1126/science.1190897
chicago: Busskamp, Volker, Jens Duebel, Dávid Bálya, Mathias Fradot, Tim Viney,
Sandra Siegert, Anna Groner, et al. “Genetic Reactivation of Cone Photoreceptors
Restores Visual Responses in Retinitis Pigmentosa.” Science. American Association
for the Advancement of Science, 2010. https://doi.org/10.1126/science.1190897.
ieee: V. Busskamp et al., “Genetic reactivation of cone photoreceptors restores
visual responses in retinitis pigmentosa,” Science, vol. 329, no. 5990.
American Association for the Advancement of Science, pp. 413–417, 2010.
ista: Busskamp V, Duebel J, Bálya D, Fradot M, Viney T, Siegert S, Groner A, Cabuy
E, Forster V, Seeliger M, Biel M, Humphries P, Pâques M, Mohand Saïd S, Trono
D, Deisseroth K, Sähel J, Picaud S, Roska B. 2010. Genetic reactivation of cone
photoreceptors restores visual responses in retinitis pigmentosa. Science. 329(5990),
413–417.
mla: Busskamp, Volker, et al. “Genetic Reactivation of Cone Photoreceptors Restores
Visual Responses in Retinitis Pigmentosa.” Science, vol. 329, no. 5990,
American Association for the Advancement of Science, 2010, pp. 413–17, doi:10.1126/science.1190897.
short: V. Busskamp, J. Duebel, D. Bálya, M. Fradot, T. Viney, S. Siegert, A. Groner,
E. Cabuy, V. Forster, M. Seeliger, M. Biel, P. Humphries, M. Pâques, S. Mohand
Saïd, D. Trono, K. Deisseroth, J. Sähel, S. Picaud, B. Roska, Science 329 (2010)
413–417.
date_created: 2018-12-11T11:54:05Z
date_published: 2010-07-23T00:00:00Z
date_updated: 2021-01-12T06:53:17Z
day: '23'
doi: 10.1126/science.1190897
extern: 1
intvolume: ' 329'
issue: '5990'
month: '07'
page: 413 - 417
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5310'
quality_controlled: 0
status: public
title: Genetic reactivation of cone photoreceptors restores visual responses in retinitis
pigmentosa
type: journal_article
volume: 329
year: '2010'
...
---
_id: '1798'
abstract:
- lang: eng
text: The mammalian brain is assembled from thousands of neuronal cell types that
are organized in distinct circuits to perform behaviorally relevant computations.
Transgenic mouse lines with selectively marked cell types would facilitate our
ability to dissect functional components of complex circuits. We carried out a
screen for cell type-specific green fluorescent protein expression in the retina
using BAC transgenic mice from the GENSAT project. Among others, we identified
mouse lines in which the inhibitory cell types of the night vision and directional
selective circuit were selectively labeled. We quantified the stratification patterns
to predict potential synaptic connectivity between marked cells of different lines
and found that some of the lines enabled targeted recordings and imaging of cell
types from developing or mature retinal circuits. Our results suggest the potential
use of a stratification-based screening approach for characterizing neuronal circuitry
in other layered brain structures, such as the neocortex.
acknowledgement: This study was supported by Friedrich Miescher Institute funds, a
US Office of Naval Research Naval International Cooperative Opportunities in Science
and Technology Program grant, a Marie Curie Excellence grant, a National Center
for Competence in Research in Genetics grant and a European Union HEALTH-F2-223156
grant to B.R., and by National Institute of Neurological Disorders and Stroke contracts
N01NS02331 and HHSN271200723701C to N.H.
author:
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Brigitte
full_name: Scherf, Brigitte G
last_name: Scherf
- first_name: Karina
full_name: Del Punta, Karina
last_name: Del Punta
- first_name: Nick
full_name: Didkovsky, Nick
last_name: Didkovsky
- first_name: Nathaniel
full_name: Heintz, Nathaniel M
last_name: Heintz
- first_name: Botond
full_name: Roska, Botond M
last_name: Roska
citation:
ama: Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. Genetic address
book for retinal cell types. Nature Neuroscience. 2009;12(9):1197-1204.
doi:10.1038/nn.2370
apa: Siegert, S., Scherf, B., Del Punta, K., Didkovsky, N., Heintz, N., & Roska,
B. (2009). Genetic address book for retinal cell types. Nature Neuroscience.
Nature Publishing Group. https://doi.org/10.1038/nn.2370
chicago: Siegert, Sandra, Brigitte Scherf, Karina Del Punta, Nick Didkovsky, Nathaniel
Heintz, and Botond Roska. “Genetic Address Book for Retinal Cell Types.” Nature
Neuroscience. Nature Publishing Group, 2009. https://doi.org/10.1038/nn.2370.
ieee: S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, and B. Roska,
“Genetic address book for retinal cell types,” Nature Neuroscience, vol.
12, no. 9. Nature Publishing Group, pp. 1197–1204, 2009.
ista: Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. 2009. Genetic
address book for retinal cell types. Nature Neuroscience. 12(9), 1197–1204.
mla: Siegert, Sandra, et al. “Genetic Address Book for Retinal Cell Types.” Nature
Neuroscience, vol. 12, no. 9, Nature Publishing Group, 2009, pp. 1197–204,
doi:10.1038/nn.2370.
short: S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, B. Roska, Nature
Neuroscience 12 (2009) 1197–1204.
date_created: 2018-12-11T11:54:04Z
date_published: 2009-09-01T00:00:00Z
date_updated: 2021-01-12T06:53:16Z
day: '01'
doi: 10.1038/nn.2370
extern: 1
intvolume: ' 12'
issue: '9'
month: '09'
page: 1197 - 1204
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '5312'
quality_controlled: 0
status: public
title: Genetic address book for retinal cell types
type: journal_article
volume: 12
year: '2009'
...
---
_id: '1799'
abstract:
- lang: eng
text: 'The detection of approaching objects, such as looming predators, is necessary
for survival. Which neurons and circuits mediate this function? We combined genetic
labeling of cell types, two-photon microscopy, electrophysiology and theoretical
modeling to address this question. We identify an approach-sensitive ganglion
cell type in the mouse retina, resolve elements of its afferent neural circuit,
and describe how these confer approach sensitivity on the ganglion cell. The circuit''s
essential building block is a rapid inhibitory pathway: it selectively suppresses
responses to non-approaching objects. This rapid inhibitory pathway, which includes
AII amacrine cells connected to bipolar cells through electrical synapses, was
previously described in the context of night-time vision. In the daytime conditions
of our experiments, the same pathway conveys signals in the reverse direction.
The dual use of a neural pathway in different physiological conditions illustrates
the efficiency with which several functions can be accommodated in a single circuit.'
acknowledgement: The study was supported by Friedrich Miescher Institute funds, a
US Office of Naval Research Naval International Cooperative Opportunities in Science
and Technology program grant, a Marie Curie Excellence Grant, a Human Frontier Science
Program Young Investigator grant, a National Centers of Competence in Research in
Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., a Marie Curie
Postdoctoral Fellowship to T.A.M., the Centre National de la Recherche Scientifique
through the Unité Mixte de Recherche 8550 to R.A.d.S.
author:
- first_name: Thomas
full_name: Münch, Thomas A
last_name: Münch
- first_name: Ravá
full_name: Da Silveira, Ravá A
last_name: Da Silveira
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Tim
full_name: Viney, Tim J
last_name: Viney
- first_name: Gautam
full_name: Awatramani, Gautam B
last_name: Awatramani
- first_name: Botond
full_name: Roska, Botond M
last_name: Roska
citation:
ama: Münch T, Da Silveira R, Siegert S, Viney T, Awatramani G, Roska B. Approach
sensitivity in the retina processed by a multifunctional neural circuit. Nature
Neuroscience. 2009;12(10):1308-1316. doi:10.1038/nn.2389
apa: Münch, T., Da Silveira, R., Siegert, S., Viney, T., Awatramani, G., & Roska,
B. (2009). Approach sensitivity in the retina processed by a multifunctional neural
circuit. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.2389
chicago: Münch, Thomas, Ravá Da Silveira, Sandra Siegert, Tim Viney, Gautam Awatramani,
and Botond Roska. “Approach Sensitivity in the Retina Processed by a Multifunctional
Neural Circuit.” Nature Neuroscience. Nature Publishing Group, 2009. https://doi.org/10.1038/nn.2389.
ieee: T. Münch, R. Da Silveira, S. Siegert, T. Viney, G. Awatramani, and B. Roska,
“Approach sensitivity in the retina processed by a multifunctional neural circuit,”
Nature Neuroscience, vol. 12, no. 10. Nature Publishing Group, pp. 1308–1316,
2009.
ista: Münch T, Da Silveira R, Siegert S, Viney T, Awatramani G, Roska B. 2009. Approach
sensitivity in the retina processed by a multifunctional neural circuit. Nature
Neuroscience. 12(10), 1308–1316.
mla: Münch, Thomas, et al. “Approach Sensitivity in the Retina Processed by a Multifunctional
Neural Circuit.” Nature Neuroscience, vol. 12, no. 10, Nature Publishing
Group, 2009, pp. 1308–16, doi:10.1038/nn.2389.
short: T. Münch, R. Da Silveira, S. Siegert, T. Viney, G. Awatramani, B. Roska,
Nature Neuroscience 12 (2009) 1308–1316.
date_created: 2018-12-11T11:54:04Z
date_published: 2009-10-01T00:00:00Z
date_updated: 2021-01-12T06:53:16Z
day: '01'
doi: 10.1038/nn.2389
extern: 1
intvolume: ' 12'
issue: '10'
month: '10'
page: 1308 - 1316
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '5311'
quality_controlled: 0
status: public
title: Approach sensitivity in the retina processed by a multifunctional neural circuit
type: journal_article
volume: 12
year: '2009'
...
---
_id: '1797'
abstract:
- lang: eng
text: Intrinsically photosensitive melanopsin-containing retinal ganglion cells
(ipRGCs) control important physiological processes, including the circadian rhythm,
the pupillary reflex, and the suppression of locomotor behavior (reviewed in [1]).
ipRGCs are also activated by classical photoreceptors, the rods and cones, through
local retinal circuits [2, 3]. ipRGCs can be transsynaptically labeled through
the pupillary-reflex circuit with the derivatives of the Bartha strain of the
alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6-12]. Bartha-strain
derivatives spread only in the retrograde direction [13]. There is evidence that
infected cells function normally for a while during GFP expression [7]. Here we
combine transsynaptic PRV labeling, two-photon laser microscopy, and electrophysiological
techniques to trace the local circuit of different ipRGC subtypes in the mouse
retina and record light-evoked activity from the transsynaptically labeled ganglion
cells. First, we show that ipRGCs are connected by monostratified amacrine cells
that provide strong inhibition from classical-photoreceptor-driven circuits. Second,
we show evidence that dopaminergic interplexiform cells are synaptically connected
to ipRGCs. The latter finding provides a circuitry link between light-dark adaptation
and ipRGC function.
acknowledgement: This study was supported by Office of Naval Research Multidisciplinary
University Research Initiative [ONR MURI] and Naval International Cooperative Opportunities
in Science and Technology Program [NICOP] grants, a Marie Curie Excellence Grant,
a Human Frontier Science Program [HFSP] Young Investigator grant, and Friedrich
Miescher Institute funds to B.R.
author:
- first_name: Tim
full_name: Viney, Tim J
last_name: Viney
- first_name: Kamill
full_name: Bálint, Kamill
last_name: Bálint
- first_name: Dániel
full_name: Hillier, Dániel
last_name: Hillier
- first_name: Sandra
full_name: Sandra Siegert
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Zsolt
full_name: Boldogköi, Zsolt S
last_name: Boldogköi
- first_name: Lynn
full_name: Enquist, Lynn W
last_name: Enquist
- first_name: Markus
full_name: Meister, Markus
last_name: Meister
- first_name: Constance
full_name: Cepko, Constance L
last_name: Cepko
- first_name: Botond
full_name: Roska, Botond M
last_name: Roska
citation:
ama: Viney T, Bálint K, Hillier D, et al. Local retinal circuits of melanopsin-containing
ganglion cells identified by transsynaptic viral tracing. Current Biology.
2007;17(11):981-988. doi:10.1016/j.cub.2007.04.058
apa: Viney, T., Bálint, K., Hillier, D., Siegert, S., Boldogköi, Z., Enquist, L.,
… Roska, B. (2007). Local retinal circuits of melanopsin-containing ganglion cells
identified by transsynaptic viral tracing. Current Biology. Cell Press.
https://doi.org/10.1016/j.cub.2007.04.058
chicago: Viney, Tim, Kamill Bálint, Dániel Hillier, Sandra Siegert, Zsolt Boldogköi,
Lynn Enquist, Markus Meister, Constance Cepko, and Botond Roska. “Local Retinal
Circuits of Melanopsin-Containing Ganglion Cells Identified by Transsynaptic Viral
Tracing.” Current Biology. Cell Press, 2007. https://doi.org/10.1016/j.cub.2007.04.058.
ieee: T. Viney et al., “Local retinal circuits of melanopsin-containing ganglion
cells identified by transsynaptic viral tracing,” Current Biology, vol.
17, no. 11. Cell Press, pp. 981–988, 2007.
ista: Viney T, Bálint K, Hillier D, Siegert S, Boldogköi Z, Enquist L, Meister M,
Cepko C, Roska B. 2007. Local retinal circuits of melanopsin-containing ganglion
cells identified by transsynaptic viral tracing. Current Biology. 17(11), 981–988.
mla: Viney, Tim, et al. “Local Retinal Circuits of Melanopsin-Containing Ganglion
Cells Identified by Transsynaptic Viral Tracing.” Current Biology, vol.
17, no. 11, Cell Press, 2007, pp. 981–88, doi:10.1016/j.cub.2007.04.058.
short: T. Viney, K. Bálint, D. Hillier, S. Siegert, Z. Boldogköi, L. Enquist, M.
Meister, C. Cepko, B. Roska, Current Biology 17 (2007) 981–988.
date_created: 2018-12-11T11:54:04Z
date_published: 2007-06-05T00:00:00Z
date_updated: 2021-01-12T06:53:15Z
day: '05'
doi: 10.1016/j.cub.2007.04.058
extern: 1
intvolume: ' 17'
issue: '11'
month: '06'
page: 981 - 988
publication: Current Biology
publication_status: published
publisher: Cell Press
publist_id: '5313'
quality_controlled: 0
status: public
title: Local retinal circuits of melanopsin-containing ganglion cells identified by
transsynaptic viral tracing
type: journal_article
volume: 17
year: '2007'
...