Sex-specific expression of distinct serotonin receptors mediates stress vulnerability of adult hippocampal neural stem cells in mice.

ABSTRACT: Women are more vulnerable to stress and have a higher likelihood of developing mood disorders. The serotonin (5HT) system has been highly implicated in stress response and mood regulation. However, sex-dependent mechanisms underlying serotonergic regulation of stress vulnerability remain poorly understood. Here, we report that adult hippocampal neural stem cells (NSCs) of the Ascl1 lineage (Ascl1-NSCs) in female mice express functional 5HT1A receptors (5HT1ARs), and selective deletion of 5HT1ARs in Ascl1-NSCs decreases the Ascl1-NSC pool only in females. Mechanistically, 5HT1AR deletion in Ascl1-NSCs of females leads to 5HT-induced depolarization mediated by upregulation of 5HT7Rs. Furthermore, repeated restraint stress (RRS) impairs Ascl1-NSC maintenance through a 5HT1AR-mediated mechanis

SUBMITTER: Luo YJ 

PROVIDER: S-EPMC11193935 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature