---
_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.
    <i>iScience</i>. 2023;26(10). doi:<a href="https://doi.org/10.1016/j.isci.2023.107780">10.1016/j.isci.2023.107780</a>
  apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino,
    A., Pohl, E. E., &#38; Siegert, S. (2023). Mitochondrial network adaptations of
    microglia reveal sex-specific stress response after injury and UCP2 knockout.
    <i>IScience</i>. Elsevier. <a href="https://doi.org/10.1016/j.isci.2023.107780">https://doi.org/10.1016/j.isci.2023.107780</a>
  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.” <i>IScience</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.isci.2023.107780">https://doi.org/10.1016/j.isci.2023.107780</a>.
  ieee: M. E. Maes <i>et al.</i>, “Mitochondrial network adaptations of microglia
    reveal sex-specific stress response after injury and UCP2 knockout,” <i>iScience</i>,
    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.” <i>IScience</i>,
    vol. 26, no. 10, 107780, Elsevier, 2023, doi:<a href="https://doi.org/10.1016/j.isci.2023.107780">10.1016/j.isci.2023.107780</a>.
  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. <i>Nature Biotechnology</i>. 2023. doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>
  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. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>
  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.” <i>Nature Biotechnology</i>. Springer
    Nature, 2023. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter
    to nanometer scales,” <i>Nature Biotechnology</i>. 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.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>.
  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. <i>iScience</i>.
    2022;25(7). doi:<a href="https://doi.org/10.1016/j.isci.2022.104580">10.1016/j.isci.2022.104580</a>
  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. <i>IScience</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.isci.2022.104580">https://doi.org/10.1016/j.isci.2022.104580</a>
  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.” <i>IScience</i>.
    Elsevier, 2022. <a href="https://doi.org/10.1016/j.isci.2022.104580">https://doi.org/10.1016/j.isci.2022.104580</a>.
  ieee: K. Bartalska <i>et al.</i>, “A systematic characterization of microglia-like
    cell occurrence during retinal organoid differentiation,” <i>iScience</i>, 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.” <i>IScience</i>, vol.
    25, no. 7, 104580, Elsevier, 2022, doi:<a href="https://doi.org/10.1016/j.isci.2022.104580">10.1016/j.isci.2022.104580</a>.
  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. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>
  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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory.
    <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>
  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.” <i>BioRxiv</i>. Cold Spring
    Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across
    scales with super-resolution light microscopy,” <i>bioRxiv</i>. 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, <a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
    with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory,
    doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  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. <i>Nature Communications</i>.
    2022;13. doi:<a href="https://doi.org/10.1038/s41467-022-32390-1">10.1038/s41467-022-32390-1</a>
  apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022).
    Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
    <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-022-32390-1">https://doi.org/10.1038/s41467-022-32390-1</a>
  chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
    Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
    Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a
    href="https://doi.org/10.1038/s41467-022-32390-1">https://doi.org/10.1038/s41467-022-32390-1</a>.
  ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
    GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature
    Communications</i>, 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.” <i>Nature Communications</i>, vol. 13, 4728, Springer
    Nature, 2022, doi:<a href="https://doi.org/10.1038/s41467-022-32390-1">10.1038/s41467-022-32390-1</a>.
  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:
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  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
  relation: main_file
  success: 1
file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
language:
- iso: eng
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: '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. <i>Nature Neuroscience</i>.
    2022;25(10):1379-1393. doi:<a href="https://doi.org/10.1038/s41593-022-01167-6">10.1038/s41593-022-01167-6</a>
  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. <i>Nature Neuroscience</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41593-022-01167-6">https://doi.org/10.1038/s41593-022-01167-6</a>
  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.” <i>Nature
    Neuroscience</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41593-022-01167-6">https://doi.org/10.1038/s41593-022-01167-6</a>.
  ieee: G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs,
    reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>,
    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.” <i>Nature Neuroscience</i>,
    vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href="https://doi.org/10.1038/s41593-022-01167-6">10.1038/s41593-022-01167-6</a>.
  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:
- access_level: open_access
  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. <i>Cell Reports</i>. 2021;36(1). doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>
  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.
    <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>
  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.” <i>Cell Reports</i>. Elsevier,
    2021. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>.
  ieee: A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly
    upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,”
    <i>Cell Reports</i>, 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.”
    <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>.
  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. <i>STAR Protocols</i>.
    2021;2(4). doi:<a href="https://doi.org/10.1016/j.xpro.2021.101012">10.1016/j.xpro.2021.101012</a>
  apa: Venturino, A., &#38; Siegert, S. (2021). Minimally invasive protocols and quantification
    for microglia-mediated perineuronal net disassembly in mouse brain. <i>STAR Protocols</i>.
    Elsevier ; Cell Press. <a href="https://doi.org/10.1016/j.xpro.2021.101012">https://doi.org/10.1016/j.xpro.2021.101012</a>
  chicago: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols
    and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse
    Brain.” <i>STAR Protocols</i>. Elsevier ; Cell Press, 2021. <a href="https://doi.org/10.1016/j.xpro.2021.101012">https://doi.org/10.1016/j.xpro.2021.101012</a>.
  ieee: A. Venturino and S. Siegert, “Minimally invasive protocols and quantification
    for microglia-mediated perineuronal net disassembly in mouse brain,” <i>STAR Protocols</i>,
    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.”
    <i>STAR Protocols</i>, vol. 2, no. 4, 101012, Elsevier ; Cell Press, 2021, doi:<a
    href="https://doi.org/10.1016/j.xpro.2021.101012">10.1016/j.xpro.2021.101012</a>.
  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'
...
