Hippocampal astrocytes induce sex-dimorphic effects on memory.

TitleHippocampal astrocytes induce sex-dimorphic effects on memory.
Publication TypeJournal Article
Year of Publication2024
AuthorsMeadows SM, Palaguachi F, Jang MWendy, Licht-Murava A, Barnett D, Zimmer TS, Zhou C, McDonough SR, Orr AL, Orr AG
JournalCell Rep
Volume43
Issue6
Pagination114278
Date Published2024 Jun 25
ISSN2211-1247
KeywordsAnimals, Astrocytes, Female, Hippocampus, Male, Memory, Mice, Mice, Inbred C57BL, Receptors, Metabotropic Glutamate, Sex Characteristics, Spatial Memory
Abstract

Astrocytic receptors influence cognitive function and can promote behavioral deficits in disease. These effects may vary based on variables such as biological sex, but it is not known if the effects of astrocytic receptors are dependent on sex. We leveraged in vivo gene editing and chemogenetics to examine the roles of astrocytic receptors in spatial memory and other processes. We show that reductions in metabotropic glutamate receptor 3 (mGluR3), the main astrocytic glutamate receptor in adults, impair memory in females but enhance memory in males. Similarly, increases in astrocytic mGluR3 levels have sex-dependent effects and enhance memory in females. mGluR3 manipulations also alter spatial search strategies during recall in a sex-specific manner. In addition, acute chemogenetic stimulation of Gi/o-coupled or Gs-coupled receptors in hippocampal astrocytes induces bidirectional and sex-dimorphic effects on memory. Thus, astrocytes are sex-dependent modulators of cognitive function and may promote sex differences in aging and disease.

DOI10.1016/j.celrep.2024.114278
Alternate JournalCell Rep
PubMed ID38795347
PubMed Central IDPMC11234507
Grant ListR00 AG048222 / AG / NIA NIH HHS / United States
RF1 NS118569 / NS / NINDS NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States