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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1564851
The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents
Provisionally accepted- 1 Beijing Institute of Basic Medical Sciences, Beijing, China
- 2 Beijing Institute of Pharmacology & Toxicology, Beijing, China
- 3 Capital Medical University, Beijing, Beijing Municipality, China
There is increasing evidence that astrocytes are involved in the therapeutic action of antidepressants. The fast antidepressant YL-0919 may interact with activation of astrocytic sigma-1 receptors (sigma-1R). In this study, function of astrocytic sigma-1R in ventral hippocampus (vHIP) mediating the rapid antidepressant effect of YL-0919 were investigated. Adeno-associated virus (AAV) expressing shRNA was constructed to knock down astrocytic sigma-1R in vHIP, and the role of astrocytic sigma-1R on the rapid antidepressant action of YL-0919 were tested in chronic restraint stress (CRS) model of mice. Small interfering RNA (siRNA) was used to knock down sigma-1R in primary astrocytes, and we explored the mitochondrial function and BDNF expression of primary astrocytes after YL-0919 and siRNA treatments. The results indicated knocking down astrocytic sigma-1R in vHIP induced anxiety-like and depressive-like behavior in mice, and blocked the rapid anti-depressant and anxiolytic effects of YL-0919. Knocking down sigma-1R in primary astrocytes inhibited the YL-0919 induced enhancement of mitochondrial function and increased level of BDNF expression. In addition, increased BDNF in vHIP might play a role in fast antidepressant impact of YL-0919. Taken together, the data provide further evidence for a role of astrocyte receptors in the mechanisms of action of antidepressants.
Keywords: Astrocytes, sigma-1 receptor, Antidepression, YL-0919, BDNF (brain derived neurotrophic factor)
Received: 22 Jan 2025; Accepted: 03 Mar 2025.
Copyright: © 2025 Li, Chang, Zhao, Bao, Dai and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wei Dai, Beijing Institute of Pharmacology & Toxicology, Beijing, China
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