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

Cramer, Teresa; Gill, Raminder; Thirouin, Zahra S; Vaas, Markus; Sampath, Suchita; Martineau, Fanny; Noya, Sara B; Panzanelli, Patrizia; Sudharshan, Tania J J; Colameo, David; Chang, Philip K-Y; Wu, Pei You; Shi, Roy; Barker, Philip A; Brown, Steven A; Paolicelli, Rosa C; Klohs, Jan; McKinney, Rebecca Anne; Tyagarajan, Shiva K

doi:10.1126/sciadv.abj0112

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Cramer, T., Gill, R., Thirouin, Z. S., Vaas, M., Sampath, S., Martineau, F., Noya, S. B., Panzanelli, P., Sudharshan, T. J. J., Colameo, D., Chang, P. K.-Y., Wu, P. Y., Shi, R., Barker, P. A., Brown, S. A., Paolicelli, R. C., Klohs, J., McKinney, R. A., & Tyagarajan, S. K. (2022). Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia. Science Advances, 8(9), eabj0112. https://doi.org/10.1126/sciadv.abj0112

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