Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia.

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Ressource 1Download: Cramer2022_Microglia regulate synapse loss in brain ischemia.pdf (3482.03 [Ko])
State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_EBD62DFC2523
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia.
Journal
Science advances
Author(s)
Cramer T., Gill R., Thirouin Z.S., Vaas M., Sampath S., Martineau F., Noya S.B., Panzanelli P., Sudharshan TJJ, Colameo D., Chang P.K., Wu P.Y., Shi R., Barker P.A., Brown S.A., Paolicelli R.C., Klohs J., McKinney R.A., Tyagarajan S.K.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
04/03/2022
Peer-reviewed
Oui
Volume
8
Number
9
Pages
eabj0112
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75 <sup>NTR</sup> ) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO.
Pubmed
Open Access
Yes
Create date
14/03/2022 8:57
Last modification date
20/07/2022 6:14
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