---
_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: '14401'
abstract:
- lang: eng
text: "Background: \r\nPro-apoptotic BAX is a central mediator of retinal ganglion
cell (RGC) death after optic nerve damage. BAX activation occurs in two stages
including translocation of latent BAX to the mitochondrial outer membrane (MOM)
and then permeabilization of the MOM to facilitate the release of apoptotic signaling
molecules. As a critical component of RGC death, BAX is an attractive target for
neuroprotective therapies and an understanding of the kinetics of BAX activation
and the mechanisms controlling the two stages of this process in RGCs is potentially
valuable in informing the development of a neuroprotective strategy.\r\nMethods:\r\nThe
kinetics of BAX translocation were assessed by both static and live-cell imaging
of a GFP-BAX fusion protein introduced into RGCs using AAV2-mediated gene transfer
in mice. Activation of BAX was achieved using an acute optic nerve crush (ONC)
protocol. Live-cell imaging of GFP-BAX was achieved using explants of mouse retina
harvested 7 days after ONC. Kinetics of translocation in RGCs were compared to
GFP-BAX translocation in 661W tissue culture cells. Permeabilization of GFP-BAX
was assessed by staining with the 6A7 monoclonal antibody, which recognizes a
conformational change in this protein after MOM insertion. Assessment of individual
kinases associated with both stages of activation was made using small molecule
inhibitors injected into the vitreous either independently or in concert with
ONC surgery. The contribution of the Dual Leucine Zipper-JUN-N-Terminal Kinase
cascade was evaluated using mice with a double conditional knock-out of both Mkk4
and Mkk7.\r\nResults:\r\nONC induces the translocation of GFP-BAX in RGCs at a
slower rate and with less intracellular synchronicity than 661W cells, but exhibits
less variability among mitochondrial foci within a single cell. GFP-BAX was also
found to translocate in all compartments of an RGC including the dendritic arbor
and axon. Approximately 6% of translocating RGCs exhibited retrotranslocation
of BAX immediately following translocation. Unlike tissue culture cells, which
exhibit simultaneous translocation and permeabilization, RGCs exhibited a significant
delay between these two stages, similar to detached cells undergoing anoikis.
Translocation, with minimal permeabilization could be induced in a subset of RGCs
using an inhibitor of Focal Adhesion Kinase (PF573228). Permeabilization after
ONC, in a majority of RGCs, could be inhibited with a broad spectrum kinase inhibitor
(sunitinib) or a selective inhibitor for p38/MAPK14 (SB203580). Intervention of
DLK-JNK axis signaling abrogated GFP-BAX translocation after ONC.\r\nConclusions:\r\nA
comparison between BAX activation kinetics in tissue culture cells and in cells
of a complex tissue environment shows distinct differences indicating that caution
should be used when translating findings from one condition to the other. RGCs
exhibit both a delay between translocation and permeabilization and the ability
for translocated BAX to be retrotranslocated, suggesting several stages at which
intervention of the activation process could be exploited in the design of a therapeutic
strategy."
acknowledgement: "The authors would like to thank Mr. Joel Dietz for management of
the mouse colony and helpful advice for conducting quantitative PCR studies and
Mr. Santoshi Kinoshita at the Translational Research Initiative in Pathology laboratory
at the University of Wisconsin-Madison for cutting sections analyzed in this study.\r\nThis
work was supported by National Eye Institute grants R01 EY030123 (RWN), R01 EY018606
(RTL), P30 EY016665 (Department of Ophthalmology and Visual Sciences, University
of Wisconsin-Madison), T32 EY027721 (RJD) and F31 EY030739 (OJM). Additional funding
was provided by the BrightFocus Foundation (RWN) and unrestricted grants from Research
to Prevent Blindness, Inc to the Department of Ophthalmology and Visual Sciences
(University of Wisconsin-Madison) and to the Department of Ophthalmology (University
of Rochester)."
article_number: '67'
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: Ryan J.
full_name: Donahue, Ryan J.
last_name: Donahue
- first_name: Cassandra L.
full_name: Schlamp, Cassandra L.
last_name: Schlamp
- first_name: Olivia J.
full_name: Marola, Olivia J.
last_name: Marola
- first_name: Richard T.
full_name: Libby, Richard T.
last_name: Libby
- first_name: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. BAX activation
in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct
steps. Molecular Neurodegeneration. 2023;18. doi:10.1186/s13024-023-00659-8
apa: Maes, M. E., Donahue, R. J., Schlamp, C. L., Marola, O. J., Libby, R. T., &
Nickells, R. W. (2023). BAX activation in mouse retinal ganglion cells occurs
in two temporally and mechanistically distinct steps. Molecular Neurodegeneration.
Springer Nature. https://doi.org/10.1186/s13024-023-00659-8
chicago: Maes, Margaret E, Ryan J. Donahue, Cassandra L. Schlamp, Olivia J. Marola,
Richard T. Libby, and Robert W. Nickells. “BAX Activation in Mouse Retinal Ganglion
Cells Occurs in Two Temporally and Mechanistically Distinct Steps.” Molecular
Neurodegeneration. Springer Nature, 2023. https://doi.org/10.1186/s13024-023-00659-8.
ieee: M. E. Maes, R. J. Donahue, C. L. Schlamp, O. J. Marola, R. T. Libby, and R.
W. Nickells, “BAX activation in mouse retinal ganglion cells occurs in two temporally
and mechanistically distinct steps,” Molecular Neurodegeneration, vol.
18. Springer Nature, 2023.
ista: Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. 2023. BAX
activation in mouse retinal ganglion cells occurs in two temporally and mechanistically
distinct steps. Molecular Neurodegeneration. 18, 67.
mla: Maes, Margaret E., et al. “BAX Activation in Mouse Retinal Ganglion Cells Occurs
in Two Temporally and Mechanistically Distinct Steps.” Molecular Neurodegeneration,
vol. 18, 67, Springer Nature, 2023, doi:10.1186/s13024-023-00659-8.
short: M.E. Maes, R.J. Donahue, C.L. Schlamp, O.J. Marola, R.T. Libby, R.W. Nickells,
Molecular Neurodegeneration 18 (2023).
date_created: 2023-10-08T22:01:15Z
date_published: 2023-09-26T00:00:00Z
date_updated: 2024-01-30T14:34:21Z
day: '26'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1186/s13024-023-00659-8
external_id:
isi:
- '001071403800001'
pmid:
- '37292963'
file:
- access_level: open_access
checksum: 3aa218ddea4a082d8fd5e196ae55ca06
content_type: application/pdf
creator: dernst
date_created: 2024-01-30T14:33:31Z
date_updated: 2024-01-30T14:33:31Z
file_id: '14917'
file_name: 2023_MolecularNeurodegeneration_Maes.pdf
file_size: 11568350
relation: main_file
success: 1
file_date_updated: 2024-01-30T14:33:31Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Neurodegeneration
publication_identifier:
eissn:
- 1750-1326
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: BAX activation in mouse retinal ganglion cells occurs in two temporally and
mechanistically distinct steps
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: 18
year: '2023'
...
---
_id: '9009'
abstract:
- lang: eng
text: Recent advancements in live cell imaging technologies have identified the
phenomenon of intracellular propagation of late apoptotic events, such as cytochrome
c release and caspase activation. The mechanism, prevalence, and speed of apoptosis
propagation remain unclear. Additionally, no studies have demonstrated propagation
of the pro-apoptotic protein, BAX. To evaluate the role of BAX in intracellular
apoptotic propagation, we used high speed live-cell imaging to visualize fluorescently
tagged-BAX recruitment to mitochondria in four immortalized cell lines. We show
that propagation of mitochondrial BAX recruitment occurs in parallel to cytochrome
c and SMAC/Diablo release and is affected by cellular morphology, such that cells
with processes are more likely to exhibit propagation. The initiation of propagation
events is most prevalent in the distal tips of processes, while the rate of propagation
is influenced by the 2-dimensional width of the process. Propagation was rarely
observed in the cell soma, which exhibited near synchronous recruitment of BAX.
Propagation velocity is not affected by mitochondrial volume in segments of processes,
but is negatively affected by mitochondrial density. There was no evidence of
a propagating wave of increased levels of intracellular calcium ions. Alternatively,
we did observe a uniform increase in superoxide build-up in cellular mitochondria,
which was released as a propagating wave simultaneously with the propagating recruitment
of BAX to the mitochondrial outer membrane.
acknowledgement: This work was supported by National Institute of Health grants R01
EY030123, P30 EY016665, and T32 GM081061, an unrestricted research grant from Research
to Prevent Blindness, Inc., and the Frederick A. Davis Endowment from the Department
of Ophthalmology and Visual Sciences at the University of Wisconsin-Madison.
article_processing_charge: No
article_type: original
author:
- first_name: Joshua A.
full_name: Grosser, Joshua A.
last_name: Grosser
- 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: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Grosser JA, Maes ME, Nickells RW. Characteristics of intracellular propagation
of mitochondrial BAX recruitment during apoptosis. Apoptosis. 2021;26(2):132-145.
doi:10.1007/s10495-020-01654-w
apa: Grosser, J. A., Maes, M. E., & Nickells, R. W. (2021). Characteristics
of intracellular propagation of mitochondrial BAX recruitment during apoptosis.
Apoptosis. Springer Nature. https://doi.org/10.1007/s10495-020-01654-w
chicago: Grosser, Joshua A., Margaret E Maes, and Robert W. Nickells. “Characteristics
of Intracellular Propagation of Mitochondrial BAX Recruitment during Apoptosis.”
Apoptosis. Springer Nature, 2021. https://doi.org/10.1007/s10495-020-01654-w.
ieee: J. A. Grosser, M. E. Maes, and R. W. Nickells, “Characteristics of intracellular
propagation of mitochondrial BAX recruitment during apoptosis,” Apoptosis,
vol. 26, no. 2. Springer Nature, pp. 132–145, 2021.
ista: Grosser JA, Maes ME, Nickells RW. 2021. Characteristics of intracellular propagation
of mitochondrial BAX recruitment during apoptosis. Apoptosis. 26(2), 132–145.
mla: Grosser, Joshua A., et al. “Characteristics of Intracellular Propagation of
Mitochondrial BAX Recruitment during Apoptosis.” Apoptosis, vol. 26, no.
2, Springer Nature, 2021, pp. 132–45, doi:10.1007/s10495-020-01654-w.
short: J.A. Grosser, M.E. Maes, R.W. Nickells, Apoptosis 26 (2021) 132–145.
date_created: 2021-01-17T23:01:11Z
date_published: 2021-02-01T00:00:00Z
date_updated: 2023-08-07T13:32:40Z
day: '01'
department:
- _id: SaSi
doi: 10.1007/s10495-020-01654-w
external_id:
isi:
- '000606722600001'
pmid:
- '33426618'
intvolume: ' 26'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082518/
month: '02'
oa: 1
oa_version: Submitted Version
page: 132-145
pmid: 1
publication: Apoptosis
publication_identifier:
eissn:
- 1573-675X
issn:
- 1360-8185
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Characteristics of intracellular propagation of mitochondrial BAX recruitment
during apoptosis
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 26
year: '2021'
...
---
_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: '10000'
abstract:
- lang: eng
text: Inhibition or targeted deletion of histone deacetylase 3 (HDAC3) is neuroprotective
in a variety neurodegenerative conditions, including retinal ganglion cells (RGCs)
after acute optic nerve damage. Consistent with this, induced HDAC3 expression
in cultured cells shows selective toxicity to neurons. Despite an established
role for HDAC3 in neuronal pathology, little is known regarding the mechanism
of this pathology.
acknowledgement: 'The authors thank Joel Dietz for maintaining the mice used in this
study, Satoshi Kinoshita and the Translational Research Initiative in Pathology
Laboratory at the University of Wisconsin-Madison for cutting retinal sections analyzed
in this study, and Mark Banghart for statistical review of the data analysis. Supported
by National Eye Institute Grants R01 EY012223 (RWN), R01 EY030123 (RWN), R01 EY029809
(LWG), R01 EY029809 (LWG) and a Vision Research CORE grant P30 EY016665, NRSA grant
T32 GM081061, by an unrestricted research grant from Research to Prevent Blindness,
Inc., and by a University of Wisconsin-Madison Vilas Life Cycle award and the Frederick
A. Davis Research Chair (RWN). '
article_number: '14'
article_processing_charge: Yes
article_type: original
author:
- first_name: Heather M.
full_name: Schmitt, Heather M.
last_name: Schmitt
- first_name: Rachel L.
full_name: Fehrman, Rachel L.
last_name: Fehrman
- 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: Huan
full_name: Yang, Huan
last_name: Yang
- first_name: Lian Wang
full_name: Guo, Lian Wang
last_name: Guo
- first_name: Cassandra L.
full_name: Schlamp, Cassandra L.
last_name: Schlamp
- first_name: Heather R.
full_name: Pelzel, Heather R.
last_name: Pelzel
- first_name: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Schmitt HM, Fehrman RL, Maes ME, et al. Increased susceptibility and intrinsic
apoptotic signaling in neurons by induced HDAC3 expression. Investigative Ophthalmology
and Visual Science. 2021;62(10). doi:10.1167/IOVS.62.10.14
apa: Schmitt, H. M., Fehrman, R. L., Maes, M. E., Yang, H., Guo, L. W., Schlamp,
C. L., … Nickells, R. W. (2021). Increased susceptibility and intrinsic apoptotic
signaling in neurons by induced HDAC3 expression. Investigative Ophthalmology
and Visual Science. Association for Research in Vision and Ophthalmology.
https://doi.org/10.1167/IOVS.62.10.14
chicago: Schmitt, Heather M., Rachel L. Fehrman, Margaret E Maes, Huan Yang, Lian
Wang Guo, Cassandra L. Schlamp, Heather R. Pelzel, and Robert W. Nickells. “Increased
Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.”
Investigative Ophthalmology and Visual Science. Association for Research
in Vision and Ophthalmology, 2021. https://doi.org/10.1167/IOVS.62.10.14.
ieee: H. M. Schmitt et al., “Increased susceptibility and intrinsic apoptotic
signaling in neurons by induced HDAC3 expression,” Investigative Ophthalmology
and Visual Science, vol. 62, no. 10. Association for Research in Vision and
Ophthalmology, 2021.
ista: Schmitt HM, Fehrman RL, Maes ME, Yang H, Guo LW, Schlamp CL, Pelzel HR, Nickells
RW. 2021. Increased susceptibility and intrinsic apoptotic signaling in neurons
by induced HDAC3 expression. Investigative Ophthalmology and Visual Science. 62(10),
14.
mla: Schmitt, Heather M., et al. “Increased Susceptibility and Intrinsic Apoptotic
Signaling in Neurons by Induced HDAC3 Expression.” Investigative Ophthalmology
and Visual Science, vol. 62, no. 10, 14, Association for Research in Vision
and Ophthalmology, 2021, doi:10.1167/IOVS.62.10.14.
short: H.M. Schmitt, R.L. Fehrman, M.E. Maes, H. Yang, L.W. Guo, C.L. Schlamp, H.R.
Pelzel, R.W. Nickells, Investigative Ophthalmology and Visual Science 62 (2021).
date_created: 2021-09-12T22:01:23Z
date_published: 2021-08-16T00:00:00Z
date_updated: 2023-08-14T06:35:17Z
day: '16'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1167/IOVS.62.10.14
external_id:
isi:
- '000695230000014'
pmid:
- '34398198'
file:
- access_level: open_access
checksum: c430967746f653aa1ae84ee617f62b73
content_type: application/pdf
creator: dernst
date_created: 2022-05-13T07:40:15Z
date_updated: 2022-05-13T07:40:15Z
file_id: '11369'
file_name: 2021_IOVS_Schmitt.pdf
file_size: 19707796
relation: main_file
success: 1
file_date_updated: 2022-05-13T07:40:15Z
has_accepted_license: '1'
intvolume: ' 62'
isi: 1
issue: '10'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Investigative Ophthalmology and Visual Science
publication_identifier:
eissn:
- 1552-5783
issn:
- 0146-0404
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
quality_controlled: '1'
scopus_import: '1'
status: public
title: Increased susceptibility and intrinsic apoptotic signaling in neurons by induced
HDAC3 expression
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 62
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: '9761'
abstract:
- lang: eng
text: 'The important roles of mitochondrial function and dysfunction in the process
of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear
to be a highly vulnerable neuronal cell type in the central nervous system with
respect to mitochondrial dysfunction but the actual reasons for this are still
incompletely understood. These cells have a unique circumstance where unmyelinated
axons must bend nearly 90° to exit the eye and then cross a translaminar pressure
gradient before becoming myelinated in the optic nerve. This region, the optic
nerve head, contains some of the highest density of mitochondria present in these
cells. Glaucoma represents a perfect storm of events occurring at this location,
with a combination of changes in the translaminar pressure gradient and reassignment
of the metabolic support functions of supporting glia, which appears to apply
increased metabolic stress to the RGC axons leading to a failure of axonal transport
mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations,
particularly in genes affecting mitochondrial dynamics and mitochondrial clearance.
These mutations, which systemically affect the mitochondria in every cell, often
lead to an optic neuropathy as the sole pathologic defect in affected patients.
This review summarizes knowledge of mitochondrial structure and function, the
known energy demands of neurons in general, and places these in the context of
normal and pathological characteristics of mitochondria attributed to RGCs. '
acknowledgement: The authors are grateful to Kazuya Oikawa and Gillian McLellan for
generously sharing some of their data for this review, and to Janis Eells for helpful
comments on the manuscript.
article_number: '1593'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicole A.
full_name: Muench, Nicole A.
last_name: Muench
- first_name: Sonia
full_name: Patel, Sonia
last_name: Patel
- 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: Ryan J.
full_name: Donahue, Ryan J.
last_name: Donahue
- first_name: Akihiro
full_name: Ikeda, Akihiro
last_name: Ikeda
- first_name: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Muench NA, Patel S, Maes ME, Donahue RJ, Ikeda A, Nickells RW. The influence
of mitochondrial dynamics and function on retinal ganglion cell susceptibility
in optic nerve disease. Cells. 2021;10(7). doi:10.3390/cells10071593
apa: Muench, N. A., Patel, S., Maes, M. E., Donahue, R. J., Ikeda, A., & Nickells,
R. W. (2021). The influence of mitochondrial dynamics and function on retinal
ganglion cell susceptibility in optic nerve disease. Cells. MDPI. https://doi.org/10.3390/cells10071593
chicago: Muench, Nicole A., Sonia Patel, Margaret E Maes, Ryan J. Donahue, Akihiro
Ikeda, and Robert W. Nickells. “The Influence of Mitochondrial Dynamics and Function
on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease.” Cells.
MDPI, 2021. https://doi.org/10.3390/cells10071593.
ieee: N. A. Muench, S. Patel, M. E. Maes, R. J. Donahue, A. Ikeda, and R. W. Nickells,
“The influence of mitochondrial dynamics and function on retinal ganglion cell
susceptibility in optic nerve disease,” Cells, vol. 10, no. 7. MDPI, 2021.
ista: Muench NA, Patel S, Maes ME, Donahue RJ, Ikeda A, Nickells RW. 2021. The influence
of mitochondrial dynamics and function on retinal ganglion cell susceptibility
in optic nerve disease. Cells. 10(7), 1593.
mla: Muench, Nicole A., et al. “The Influence of Mitochondrial Dynamics and Function
on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease.” Cells,
vol. 10, no. 7, 1593, MDPI, 2021, doi:10.3390/cells10071593.
short: N.A. Muench, S. Patel, M.E. Maes, R.J. Donahue, A. Ikeda, R.W. Nickells,
Cells 10 (2021).
date_created: 2021-08-01T22:01:22Z
date_published: 2021-06-25T00:00:00Z
date_updated: 2023-08-10T14:14:53Z
day: '25'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.3390/cells10071593
external_id:
isi:
- '000678193300001'
pmid:
- '34201955'
file:
- access_level: open_access
checksum: e0497ce5c77fa3b65a538c7d6e0f6c66
content_type: application/pdf
creator: cziletti
date_created: 2021-08-04T14:01:30Z
date_updated: 2021-08-04T14:01:30Z
file_id: '9768'
file_name: 2021_Cells_Muench.pdf
file_size: 4555611
relation: main_file
success: 1
file_date_updated: 2021-08-04T14:01:30Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '7'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Cells
publication_identifier:
eissn:
- '20734409'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: The influence of mitochondrial dynamics and function on retinal ganglion cell
susceptibility in optic nerve disease
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: 10
year: '2021'
...
---
_id: '7033'
abstract:
- lang: eng
text: Removal of the Bax gene from mice completely protects the somas of retinal
ganglion cells (RGCs) from apoptosis following optic nerve injury. This makes
BAX a promising therapeutic target to prevent neurodegeneration. In this study,
Bax+/− mice were used to test the hypothesis that lowering the quantity of BAX
in RGCs would delay apoptosis following optic nerve injury. RGCs were damaged
by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN,
and quantitative PCR were used to monitor the status of the BAX activation mechanism
in the months following injury. The apoptotic susceptibility of injured cells
was directly tested by virally introducing GFP-BAX into Bax−/− RGCs after injury.
The competency of quiescent RGCs to reactivate their BAX activation mechanism
was tested by intravitreal injection of the JNK pathway agonist, anisomycin. Twenty-four
weeks after ONC, Bax+/− mice had significantly less cell loss in their RGC layer
than Bax+/+ mice 3 weeks after ONC. Bax+/− and Bax+/+ RGCs exhibited similar patterns
of nuclear phospho-cJUN accumulation immediately after ONC, which persisted in
Bax+/− RGCs for up to 7 weeks before abating. The transcriptional activation of
BAX-activating genes was similar in Bax+/− and Bax+/+ RGCs following ONC. Intriguingly,
cells deactivated their BAX activation mechanism between 7 and 12 weeks after
crush. Introduction of GFP-BAX into Bax−/− cells at 4 weeks after ONC showed that
these cells had a nearly normal capacity to activate this protein, but this capacity
was lost 8 weeks after crush. Collectively, these data suggest that 8–12 weeks
after crush, damaged cells no longer displayed increased susceptibility to BAX
activation relative to their naïve counterparts. In this same timeframe, retinal
glial activation and the signaling of the pro-apoptotic JNK pathway also abated.
Quiescent RGCs did not show a timely reactivation of their JNK pathway following
intravitreal injection with anisomycin. These findings demonstrate that lowering
the quantity of BAX in RGCs is neuroprotective after acute injury. Damaged RGCs
enter a quiescent state months after injury and are no longer responsive to an
apoptotic stimulus. Quiescent RGCs will require rejuvenation to reacquire functionality.
acknowledgement: This work was supported by National Eye Institute grants R01 EY012223
(RWN), R01 EY030123 (RWN), T32 EY027721 (Department of Ophthalmology and Visual
Sciences, University of Wisconsin-Madison), and a Vision Science Core grant P30
EY016665 (Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison),
an unrestricted funding grant from Research to Prevent Blindness (Department of
Ophthalmology and Visual Sciences, University of Wisconsin-Madison), the Frederick
A. Davis Endowment (RWN), and the Mr. and Mrs. George Taylor Foundation (RWN).
article_processing_charge: No
article_type: original
author:
- first_name: RJ
full_name: Donahue, RJ
last_name: Donahue
- 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: JA
full_name: Grosser, JA
last_name: Grosser
- first_name: RW
full_name: Nickells, RW
last_name: Nickells
citation:
ama: Donahue R, Maes ME, Grosser J, Nickells R. BAX-depleted retinal ganglion cells
survive and become quiescent following optic nerve damage. Molecular Neurobiology.
2020;57(2):1070–1084. doi:10.1007/s12035-019-01783-7
apa: Donahue, R., Maes, M. E., Grosser, J., & Nickells, R. (2020). BAX-depleted
retinal ganglion cells survive and become quiescent following optic nerve damage.
Molecular Neurobiology. Springer Nature. https://doi.org/10.1007/s12035-019-01783-7
chicago: Donahue, RJ, Margaret E Maes, JA Grosser, and RW Nickells. “BAX-Depleted
Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage.”
Molecular Neurobiology. Springer Nature, 2020. https://doi.org/10.1007/s12035-019-01783-7.
ieee: R. Donahue, M. E. Maes, J. Grosser, and R. Nickells, “BAX-depleted retinal
ganglion cells survive and become quiescent following optic nerve damage,” Molecular
Neurobiology, vol. 57, no. 2. Springer Nature, pp. 1070–1084, 2020.
ista: Donahue R, Maes ME, Grosser J, Nickells R. 2020. BAX-depleted retinal ganglion
cells survive and become quiescent following optic nerve damage. Molecular Neurobiology.
57(2), 1070–1084.
mla: Donahue, RJ, et al. “BAX-Depleted Retinal Ganglion Cells Survive and Become
Quiescent Following Optic Nerve Damage.” Molecular Neurobiology, vol. 57,
no. 2, Springer Nature, 2020, pp. 1070–1084, doi:10.1007/s12035-019-01783-7.
short: R. Donahue, M.E. Maes, J. Grosser, R. Nickells, Molecular Neurobiology 57
(2020) 1070–1084.
date_created: 2019-11-18T14:18:39Z
date_published: 2020-02-01T00:00:00Z
date_updated: 2023-08-17T14:05:48Z
day: '01'
department:
- _id: SaSi
doi: 10.1007/s12035-019-01783-7
external_id:
isi:
- '000493754200001'
pmid:
- '31673950'
intvolume: ' 57'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035206/
month: '02'
oa: 1
oa_version: Submitted Version
page: 1070–1084
pmid: 1
publication: Molecular Neurobiology
publication_identifier:
eissn:
- 1559-1182
issn:
- 0893-7648
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: BAX-depleted retinal ganglion cells survive and become quiescent following
optic nerve damage
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 57
year: '2020'
...
---
_id: '7095'
abstract:
- lang: eng
text: BAX, a member of the BCL2 gene family, controls the committed step of the
intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed
feature of apoptosis, which occurs through the process of mitochondrial fission.
BAX has consistently been associated with mitochondrial fission, yet how BAX participates
in the process of mitochondrial fragmentation during apoptosis remains to be tested.
Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates
that rapid mitochondrial fragmentation during apoptosis occurs after the complete
recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement
of a fully functioning BAX protein for the fission process was demonstrated further
in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant
performed fusion to restore the mitochondrial network. but was not demonstrably
recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial
fragmentation was blocked. Additionally, we show that loss of the fission protein,
dynamin-like protein 1 (DRP1), does not temporally affect the initiation time
or rate of BAX recruitment, but does reduce the final level of BAX recruited to
the MOM during the late phase of BAX recruitment. These correlative observations
suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial
fragmentation machinery in apoptotic cells.
article_number: '16565'
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: J. A.
full_name: Grosser, J. A.
last_name: Grosser
- first_name: R. L.
full_name: Fehrman, R. L.
last_name: Fehrman
- first_name: C. L.
full_name: Schlamp, C. L.
last_name: Schlamp
- first_name: R. W.
full_name: Nickells, R. W.
last_name: Nickells
citation:
ama: Maes ME, Grosser JA, Fehrman RL, Schlamp CL, Nickells RW. Completion of BAX
recruitment correlates with mitochondrial fission during apoptosis. Scientific
Reports. 2019;9. doi:10.1038/s41598-019-53049-w
apa: Maes, M. E., Grosser, J. A., Fehrman, R. L., Schlamp, C. L., & Nickells,
R. W. (2019). Completion of BAX recruitment correlates with mitochondrial fission
during apoptosis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-019-53049-w
chicago: Maes, Margaret E, J. A. Grosser, R. L. Fehrman, C. L. Schlamp, and R. W.
Nickells. “Completion of BAX Recruitment Correlates with Mitochondrial Fission
during Apoptosis.” Scientific Reports. Springer Nature, 2019. https://doi.org/10.1038/s41598-019-53049-w.
ieee: M. E. Maes, J. A. Grosser, R. L. Fehrman, C. L. Schlamp, and R. W. Nickells,
“Completion of BAX recruitment correlates with mitochondrial fission during apoptosis,”
Scientific Reports, vol. 9. Springer Nature, 2019.
ista: Maes ME, Grosser JA, Fehrman RL, Schlamp CL, Nickells RW. 2019. Completion
of BAX recruitment correlates with mitochondrial fission during apoptosis. Scientific
Reports. 9, 16565.
mla: Maes, Margaret E., et al. “Completion of BAX Recruitment Correlates with Mitochondrial
Fission during Apoptosis.” Scientific Reports, vol. 9, 16565, Springer
Nature, 2019, doi:10.1038/s41598-019-53049-w.
short: M.E. Maes, J.A. Grosser, R.L. Fehrman, C.L. Schlamp, R.W. Nickells, Scientific
Reports 9 (2019).
date_created: 2019-11-25T07:45:17Z
date_published: 2019-11-12T00:00:00Z
date_updated: 2023-08-30T07:26:54Z
day: '12'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41598-019-53049-w
external_id:
isi:
- '000495857600019'
pmid:
- '31719602'
file:
- access_level: open_access
checksum: 9ab397ed9c1c454b34bffb8cc863d734
content_type: application/pdf
creator: dernst
date_created: 2019-11-25T07:49:52Z
date_updated: 2020-07-14T12:47:49Z
file_id: '7096'
file_name: 2019_ScientificReports_Maes.pdf
file_size: 6467393
relation: main_file
file_date_updated: 2020-07-14T12:47:49Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Scientific Reports
publication_identifier:
eissn:
- 2045-2322
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Completion of BAX recruitment correlates with mitochondrial fission during
apoptosis
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: 9
year: '2019'
...
---
_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: '557'
abstract:
- lang: eng
text: PURPOSE. Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful
therapeutic for the rescue and regeneration of these cells after optic nerve damage.
However, early after damage, RGCs undergo atrophic changes, including gene silencing.
It is not known if these changes will deleteriously affect transduction and transgene
expression, or if the therapeutic protein can influence reactivation of the endogenous
genome. METHODS. Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter,
and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant
blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At
times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received
an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful
transduction was monitored by expression of the tdTomato reporter. Immunostaining
was used to localize tdTomato expression in select cell types. RESULTS. Successful
transduction of RGCs was achieved at all time points after ONC using AAV2 expressing
Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter.
ONC promoted an increase in the transduction of cell types in the inner nuclear
layer, including Müller cells and rod bipolar neurons. There was minimal evidence
of transduction of amacrine cells and astrocytes in the inner retina or optic
nerve. CONCLUSIONS. Damaged RGCs can be transduced and at least some endogenous
genes can be subsequently activated. Optic nerve damage may change retinal architecture
to allow greater penetration of an AAV2 virus to transduce several additional
cell types in the inner nuclear layer.
article_processing_charge: No
author:
- first_name: Robert
full_name: Nickells, Robert
last_name: Nickells
- first_name: Heather
full_name: Schmitt, Heather
last_name: Schmitt
- 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: Cassandra
full_name: Schlamp, Cassandra
last_name: Schlamp
citation:
ama: Nickells R, Schmitt H, Maes ME, Schlamp C. AAV2 mediated transduction of the
mouse retina after optic nerve injury. Investigative Ophthalmology and Visual
Science. 2017;58(14):6091-6104. doi:10.1167/iovs.17-22634
apa: Nickells, R., Schmitt, H., Maes, M. E., & Schlamp, C. (2017). AAV2 mediated
transduction of the mouse retina after optic nerve injury. Investigative Ophthalmology
and Visual Science. Association for Research in Vision and Ophthalmology.
https://doi.org/10.1167/iovs.17-22634
chicago: Nickells, Robert, Heather Schmitt, Margaret E Maes, and Cassandra Schlamp.
“AAV2 Mediated Transduction of the Mouse Retina after Optic Nerve Injury.” Investigative
Ophthalmology and Visual Science. Association for Research in Vision and Ophthalmology,
2017. https://doi.org/10.1167/iovs.17-22634.
ieee: R. Nickells, H. Schmitt, M. E. Maes, and C. Schlamp, “AAV2 mediated transduction
of the mouse retina after optic nerve injury,” Investigative Ophthalmology
and Visual Science, vol. 58, no. 14. Association for Research in Vision and
Ophthalmology, pp. 6091–6104, 2017.
ista: Nickells R, Schmitt H, Maes ME, Schlamp C. 2017. AAV2 mediated transduction
of the mouse retina after optic nerve injury. Investigative Ophthalmology and
Visual Science. 58(14), 6091–6104.
mla: Nickells, Robert, et al. “AAV2 Mediated Transduction of the Mouse Retina after
Optic Nerve Injury.” Investigative Ophthalmology and Visual Science, vol.
58, no. 14, Association for Research in Vision and Ophthalmology, 2017, pp. 6091–104,
doi:10.1167/iovs.17-22634.
short: R. Nickells, H. Schmitt, M.E. Maes, C. Schlamp, Investigative Ophthalmology
and Visual Science 58 (2017) 6091–6104.
date_created: 2018-12-11T11:47:10Z
date_published: 2017-12-14T00:00:00Z
date_updated: 2023-10-10T14:06:18Z
day: '14'
ddc:
- '576'
department:
- _id: SaSi
doi: 10.1167/iovs.17-22634
file:
- access_level: open_access
checksum: d7a7b6f1fa9211a04e5e65634a0265d9
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:53Z
date_updated: 2020-07-14T12:47:04Z
file_id: '5311'
file_name: IST-2018-920-v1+1_i1552-5783-58-14-6091.pdf
file_size: 2955559
relation: main_file
file_date_updated: 2020-07-14T12:47:04Z
has_accepted_license: '1'
intvolume: ' 58'
issue: '14'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 6091 - 6104
publication: Investigative Ophthalmology and Visual Science
publication_identifier:
issn:
- '01460404'
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
publist_id: '7254'
pubrep_id: '920'
quality_controlled: '1'
scopus_import: '1'
status: public
title: AAV2 mediated transduction of the mouse retina after optic nerve injury
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: 58
year: '2017'
...