Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons
Abstract Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in...
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| Language: | English |
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BMC
2024-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-06020-x |
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| author | Kedong Zhu Lanxia Meng Jiaying Luo Tingting Wen Liang Dan Zhihao Wang Xuebing Cao Zhaohui Zhang Guiqin Chen |
| author_facet | Kedong Zhu Lanxia Meng Jiaying Luo Tingting Wen Liang Dan Zhihao Wang Xuebing Cao Zhaohui Zhang Guiqin Chen |
| author_sort | Kedong Zhu |
| collection | DOAJ |
| description | Abstract Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in vivo and in vitro methods, including transcriptomic analysis, were employed to elucidate the effects of Taltirelin on cellular composition and signaling pathways in the striatum of hemi-PD rats. We demonstrated that Taltirelin upregulates the expression of TRHR on striatal GABAergic neurons, which is accompanied by activation of the TRHR-MAPK-RARα-DRD2 pathway. Consequently, Taltirelin induces medium spiny neurons in the striatum to express TH. This discovery provides valuable insights into the potential application of Taltirelin in neurological disorders and offers new directions for drug development. |
| format | Article |
| id | doaj-art-1ad37f2ce50843ec9eb231dc2dfe5f05 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-1ad37f2ce50843ec9eb231dc2dfe5f052025-08-20T01:47:58ZengBMCJournal of Translational Medicine1479-58762024-12-0122111910.1186/s12967-024-06020-xTaltirelin induces TH expression by regulating TRHR and RARα in medium spiny neuronsKedong Zhu0Lanxia Meng1Jiaying Luo2Tingting Wen3Liang Dan4Zhihao Wang5Xuebing Cao6Zhaohui Zhang7Guiqin Chen8Department of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Union Hospital, Tongji Medical College, , Huazhong University of Science and TechnologyDepartment of Neurology, Renmin Hospital of Wuhan UniversityDepartment of Neurology, Renmin Hospital of Wuhan UniversityAbstract Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in vivo and in vitro methods, including transcriptomic analysis, were employed to elucidate the effects of Taltirelin on cellular composition and signaling pathways in the striatum of hemi-PD rats. We demonstrated that Taltirelin upregulates the expression of TRHR on striatal GABAergic neurons, which is accompanied by activation of the TRHR-MAPK-RARα-DRD2 pathway. Consequently, Taltirelin induces medium spiny neurons in the striatum to express TH. This discovery provides valuable insights into the potential application of Taltirelin in neurological disorders and offers new directions for drug development.https://doi.org/10.1186/s12967-024-06020-xTaltirelinDopamine receptor D2Tyrosine hydroxylaseThyrotropin-releasing hormone receptor |
| spellingShingle | Kedong Zhu Lanxia Meng Jiaying Luo Tingting Wen Liang Dan Zhihao Wang Xuebing Cao Zhaohui Zhang Guiqin Chen Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons Journal of Translational Medicine Taltirelin Dopamine receptor D2 Tyrosine hydroxylase Thyrotropin-releasing hormone receptor |
| title | Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons |
| title_full | Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons |
| title_fullStr | Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons |
| title_full_unstemmed | Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons |
| title_short | Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons |
| title_sort | taltirelin induces th expression by regulating trhr and rarα in medium spiny neurons |
| topic | Taltirelin Dopamine receptor D2 Tyrosine hydroxylase Thyrotropin-releasing hormone receptor |
| url | https://doi.org/10.1186/s12967-024-06020-x |
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