Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum
Abstract The circadian rhythm system consists of a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks dispersed throughout other brain areas (including striatum, Str) as well as various tissues and organs. Circadian rhythm disturbance is a major risk...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-03-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03313-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850054277879300096 |
|---|---|
| author | Xiaotao Liang Yuewen Ding Xiaoyu Zhu Jing Qiu Xiaoqin Shen Yifan Xiong Jieli Zhou Xiaoshan Liang Wei Xie |
| author_facet | Xiaotao Liang Yuewen Ding Xiaoyu Zhu Jing Qiu Xiaoqin Shen Yifan Xiong Jieli Zhou Xiaoshan Liang Wei Xie |
| author_sort | Xiaotao Liang |
| collection | DOAJ |
| description | Abstract The circadian rhythm system consists of a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks dispersed throughout other brain areas (including striatum, Str) as well as various tissues and organs. Circadian rhythm disturbance is a major risk factor and common comorbidity for mood disorders, especially anxiety and depression. Bmal1 is one of the fundamental clock protein genes that is required to maintain circadian rhythm. Recent research has revealed a link between suprachiasmatic nucleus dysfunction and anxiety and depression, but the underlying mechanisms remain to be fully elucidated. This study aimed to investigate how circadian rhythm disturbance may lead to anxiety- and depression-like behaviors. Through behavioral tests, virus tracing, molecular biology and other techniques, we found neural connection from the suprachiasmatic nucleus to the striatum. SCN lesions and Bmal1flox/flox + pAAV-hSyn-Cre-GFP (conditional knockout, cKO) mice exhibited disruptions in core body temperature rhythm, as well as anxiety- and depression-like behaviors. Importantly, these mice displayed altered expression patterns of clock protein genes and an upregulation of the Brain-Derived Neurotrophic Factor (BDNF) - Tyrosine Kinase receptor B (TrkB) signaling pathway within the striatum. Microinjection of the TrkB inhibitor ANA-12 can effectively reverse anxiety- and depression-like behaviors. These findings indicate that suprachiasmatic nucleus dysfunction may contribute to the pathogenesis of anxiety and depression through upregulation of the BDNF-TrkB pathway in the striatum, potentially mediated by neural projections from the SCN. Bmal1 gene within SCN may represent a novel therapeutic target for mood disorders. |
| format | Article |
| id | doaj-art-32fde970abc04d77aa288ea4ea2b68a6 |
| institution | DOAJ |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-32fde970abc04d77aa288ea4ea2b68a62025-08-20T02:52:19ZengNature Publishing GroupTranslational Psychiatry2158-31882025-03-0115111210.1038/s41398-025-03313-7Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatumXiaotao Liang0Yuewen Ding1Xiaoyu Zhu2Jing Qiu3Xiaoqin Shen4Yifan Xiong5Jieli Zhou6Xiaoshan Liang7Wei Xie8School of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversityDepartment of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical UniversitySchool of Traditional Chinese Medicine, Southern Medical UniversityAbstract The circadian rhythm system consists of a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks dispersed throughout other brain areas (including striatum, Str) as well as various tissues and organs. Circadian rhythm disturbance is a major risk factor and common comorbidity for mood disorders, especially anxiety and depression. Bmal1 is one of the fundamental clock protein genes that is required to maintain circadian rhythm. Recent research has revealed a link between suprachiasmatic nucleus dysfunction and anxiety and depression, but the underlying mechanisms remain to be fully elucidated. This study aimed to investigate how circadian rhythm disturbance may lead to anxiety- and depression-like behaviors. Through behavioral tests, virus tracing, molecular biology and other techniques, we found neural connection from the suprachiasmatic nucleus to the striatum. SCN lesions and Bmal1flox/flox + pAAV-hSyn-Cre-GFP (conditional knockout, cKO) mice exhibited disruptions in core body temperature rhythm, as well as anxiety- and depression-like behaviors. Importantly, these mice displayed altered expression patterns of clock protein genes and an upregulation of the Brain-Derived Neurotrophic Factor (BDNF) - Tyrosine Kinase receptor B (TrkB) signaling pathway within the striatum. Microinjection of the TrkB inhibitor ANA-12 can effectively reverse anxiety- and depression-like behaviors. These findings indicate that suprachiasmatic nucleus dysfunction may contribute to the pathogenesis of anxiety and depression through upregulation of the BDNF-TrkB pathway in the striatum, potentially mediated by neural projections from the SCN. Bmal1 gene within SCN may represent a novel therapeutic target for mood disorders.https://doi.org/10.1038/s41398-025-03313-7 |
| spellingShingle | Xiaotao Liang Yuewen Ding Xiaoyu Zhu Jing Qiu Xiaoqin Shen Yifan Xiong Jieli Zhou Xiaoshan Liang Wei Xie Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum Translational Psychiatry |
| title | Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum |
| title_full | Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum |
| title_fullStr | Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum |
| title_full_unstemmed | Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum |
| title_short | Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum |
| title_sort | suprachiasmatic nucleus dysfunction induces anxiety and depression like behaviors via activating the bdnf trkb pathway of the striatum |
| url | https://doi.org/10.1038/s41398-025-03313-7 |
| work_keys_str_mv | AT xiaotaoliang suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT yuewending suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT xiaoyuzhu suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT jingqiu suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT xiaoqinshen suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT yifanxiong suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT jielizhou suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT xiaoshanliang suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum AT weixie suprachiasmaticnucleusdysfunctioninducesanxietyanddepressionlikebehaviorsviaactivatingthebdnftrkbpathwayofthestriatum |