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

Yan-Jia Luo; Hechen Bao; Andrew Crowther; Ya-Dong Li; Ze-Ka Chen; Dalton S. Tart; Brent Asrican; Libo Zhang; Juan Song

Cell Reports (May 2024)

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

Yan-Jia Luo,
Hechen Bao,
Andrew Crowther,
Ya-Dong Li,
Ze-Ka Chen,
Dalton S. Tart,
Brent Asrican,
Libo Zhang,
Juan Song

Affiliations

Yan-Jia Luo: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Anesthesiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Hechen Bao: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA
Andrew Crowther: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA
Ya-Dong Li: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Songjiang Research Institute, Songjiang Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai 201699, China
Ze-Ka Chen: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA
Dalton S. Tart: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA
Brent Asrican: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA
Libo Zhang: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA
Juan Song: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 5
p. 114140

Abstract

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Summary: 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 mechanism. By contrast, Ascl1-NSCs in males express 5HT7R receptors (5HT7Rs) that are downregulated by RRS, thus maintaining the Ascl1-NSC pool. These findings suggest that sex-specific expression of distinct 5HTRs and their differential interactions with stress may underlie sex differences in stress vulnerability.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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