Title | Hippocampal astrocytes induce sex-dimorphic effects on memory. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Meadows SM, Palaguachi F, Jang MWendy, Licht-Murava A, Barnett D, Zimmer TS, Zhou C, McDonough SR, Orr AL, Orr AG |
Journal | Cell Rep |
Volume | 43 |
Issue | 6 |
Pagination | 114278 |
Date Published | 2024 Jun 25 |
ISSN | 2211-1247 |
Keywords | Animals, 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. |
DOI | 10.1016/j.celrep.2024.114278 |
Alternate Journal | Cell Rep |
PubMed ID | 38795347 |
PubMed Central ID | PMC11234507 |
Grant List | R00 AG048222 / AG / NIA NIH HHS / United States RF1 NS118569 / NS / NINDS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |