The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents
Introduction: 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).Methods: In this study, function of astrocytic sigma-1R in ventral hippocampus...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564851/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849339948838158336 |
|---|---|
| author | Jin-Feng Li Jin-Feng Li Hai-Xia Chang Jia-Ning Zhao Jia-Ning Zhao Jin-Hao Bao Wei Dai Yun-Feng Li Yun-Feng Li |
| author_facet | Jin-Feng Li Jin-Feng Li Hai-Xia Chang Jia-Ning Zhao Jia-Ning Zhao Jin-Hao Bao Wei Dai Yun-Feng Li Yun-Feng Li |
| author_sort | Jin-Feng Li |
| collection | DOAJ |
| description | Introduction: 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).Methods: 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. Result: 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.Conclusion: Taken together, these results reveal increased BDNF in vHIP by affecting glial cells might be one of the significant mechanisms of fast antidepressant effect of YL-0919. The data provide further evidence for a role of astrocyte receptors in the mechanisms of action of antidepressants. |
| format | Article |
| id | doaj-art-b18552f221b84c6cb1fb48616d40850c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-b18552f221b84c6cb1fb48616d40850c2025-08-20T03:44:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15648511564851The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodentsJin-Feng Li0Jin-Feng Li1Hai-Xia Chang2Jia-Ning Zhao3Jia-Ning Zhao4Jin-Hao Bao5Wei Dai6Yun-Feng Li7Yun-Feng Li8Beijing Institute of Basic Medical Sciences, Beijing, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaBeijing Institute of Basic Medical Sciences, Beijing, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing, ChinaShenyang Pharmaceutical University, Shenyang, ChinaSchool of Basic Medical Sciences, Capital Medical University, Beijing, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing, ChinaBeijing Institute of Basic Medical Sciences, Beijing, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing, ChinaIntroduction: 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).Methods: 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. Result: 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.Conclusion: Taken together, these results reveal increased BDNF in vHIP by affecting glial cells might be one of the significant mechanisms of fast antidepressant effect of YL-0919. The data provide further evidence for a role of astrocyte receptors in the mechanisms of action of antidepressants.https://www.frontiersin.org/articles/10.3389/fphar.2025.1564851/fullastrocytessigma-1 receptorantidepressionYL-0919brain derived neurotrophic factor (BDNF) |
| spellingShingle | Jin-Feng Li Jin-Feng Li Hai-Xia Chang Jia-Ning Zhao Jia-Ning Zhao Jin-Hao Bao Wei Dai Yun-Feng Li Yun-Feng Li The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents Frontiers in Pharmacology astrocytes sigma-1 receptor antidepression YL-0919 brain derived neurotrophic factor (BDNF) |
| title | The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents |
| title_full | The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents |
| title_fullStr | The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents |
| title_full_unstemmed | The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents |
| title_short | The astrocytic sigma-1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride (YL-0919) in rodents |
| title_sort | astrocytic sigma 1 receptor constitutes in the fast antidepressant action of hypidone hydrochloride yl 0919 in rodents |
| topic | astrocytes sigma-1 receptor antidepression YL-0919 brain derived neurotrophic factor (BDNF) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564851/full |
| work_keys_str_mv | AT jinfengli theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jinfengli theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT haixiachang theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jianingzhao theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jianingzhao theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jinhaobao theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT weidai theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT yunfengli theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT yunfengli theastrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jinfengli astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jinfengli astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT haixiachang astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jianingzhao astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jianingzhao astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT jinhaobao astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT weidai astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT yunfengli astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents AT yunfengli astrocyticsigma1receptorconstitutesinthefastantidepressantactionofhypidonehydrochlorideyl0919inrodents |