Astrocytes regulate spatial memory in a sex-specific manner

Meadows, S. M.; Palaguachi, F.; Licht-Murava, A.; Barnett, D.; Zimmer, T. S.; Zhou, C.; McDonough, S. R.; Orr, A. L.; Orr, A. G.

doi:10.1101/2022.11.03.511881

bioRxiv · 10.1101/2022.11.03.511881

Astrocytes regulate spatial memory in a sex-specific manner

Meadows, S. M.·Palaguachi, F.·Licht-Murava, A.·Barnett, D.·Zimmer, T. S.·Zhou, C.·McDonough, S. R.·Orr, A. L.·Orr, A. G.

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Abstract

Cognitive processes and neurocognitive disorders are regulated by astrocytes and have prominent sex differences. However, the contribution of astrocytes to sex differences is not known. We leveraged astrocyte-targeted gene editing and chemogenetics in adult mice to reveal that astrocytic glutamate receptors and other G protein-coupled receptors (GPCRs) modulate hippocampus-dependent cognitive function in a sexually dimorphic manner. In females, spatial memory was improved by increasing metabotropic glutamate receptor 3 (mGluR3) in astrocytes or stimulating astrocytic Gi/o-coupled signaling, whereas stimulating Gs-coupled signaling impaired memory. However, in males, memory was improved by reducing mGluR3 or stimulating Gs-coupled signaling, whereas stimulating Gi/o-coupled signaling impaired memory. Thus, memory requires a sex-specific balance of astrocytic Gs-coupled and Gi/o-coupled receptor activities, and disease-associated alterations or therapeutic targeting of these pathways may cause opposing sex-dependent effects on cognitive function. SummaryGlia cause sex-specific changes in cognition

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Meadows, S. M., Palaguachi, F., Licht-Murava, A., Barnett, D., Zimmer, T. S., Zhou, C., McDonough, S. R., Orr, A. L., Orr, A. G.. 2022-11-03. Astrocytes regulate spatial memory in a sex-specific manner. https://doi.org/10.1101/2022.11.03.511881

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