Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice
Abstract Depression and comorbid pain are frequently encountered clinically, and the comorbidity complicates the overall medical management. However, the mechanism whereby depression triggers development of pain needs to be further elucidated. Here, by using the chronic restraint stress (CRS) mouse...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07590-2 |
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| author | Xianlei Wang Shulin Wu Junsheng Zuo Keying Li Yutong Chen Zhijie Fan Zhou Wu Jun-Xia Yang Weiyi Song Jun-Li Cao Mengqiao Cui |
| author_facet | Xianlei Wang Shulin Wu Junsheng Zuo Keying Li Yutong Chen Zhijie Fan Zhou Wu Jun-Xia Yang Weiyi Song Jun-Li Cao Mengqiao Cui |
| author_sort | Xianlei Wang |
| collection | DOAJ |
| description | Abstract Depression and comorbid pain are frequently encountered clinically, and the comorbidity complicates the overall medical management. However, the mechanism whereby depression triggers development of pain needs to be further elucidated. Here, by using the chronic restraint stress (CRS) mouse model of depression and comorbid pain, we showed that CRS hyperactivated the glutamatergic neurons in the anterior cingulate cortex (ACC), as well as increasing the dendrite complexity and number. Chemogenetic activation of these neurons can induce depression and pain, while chemogenetic blockade can reverse such depression-induced pain. Moreover, we utilized translating ribosome affinity purification (TRAP) in combination with c-Fos-tTA strategy and pharmacological approaches and identified SIGMAR1 as a potential therapeutic molecular target. These results revealed a previously unknown neural mechanism for depression and pain comorbidity and provided new mechanistic insights into the antidepressive and analgesic effects of the disease. |
| format | Article |
| id | doaj-art-b6790435445e44cb8aaee42545d4877e |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-b6790435445e44cb8aaee42545d4877e2025-02-02T12:37:17ZengNature PortfolioCommunications Biology2399-36422025-01-018111210.1038/s42003-025-07590-2Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male miceXianlei Wang0Shulin Wu1Junsheng Zuo2Keying Li3Yutong Chen4Zhijie Fan5Zhou Wu6Jun-Xia Yang7Weiyi Song8Jun-Li Cao9Mengqiao Cui10Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityAbstract Depression and comorbid pain are frequently encountered clinically, and the comorbidity complicates the overall medical management. However, the mechanism whereby depression triggers development of pain needs to be further elucidated. Here, by using the chronic restraint stress (CRS) mouse model of depression and comorbid pain, we showed that CRS hyperactivated the glutamatergic neurons in the anterior cingulate cortex (ACC), as well as increasing the dendrite complexity and number. Chemogenetic activation of these neurons can induce depression and pain, while chemogenetic blockade can reverse such depression-induced pain. Moreover, we utilized translating ribosome affinity purification (TRAP) in combination with c-Fos-tTA strategy and pharmacological approaches and identified SIGMAR1 as a potential therapeutic molecular target. These results revealed a previously unknown neural mechanism for depression and pain comorbidity and provided new mechanistic insights into the antidepressive and analgesic effects of the disease.https://doi.org/10.1038/s42003-025-07590-2 |
| spellingShingle | Xianlei Wang Shulin Wu Junsheng Zuo Keying Li Yutong Chen Zhijie Fan Zhou Wu Jun-Xia Yang Weiyi Song Jun-Li Cao Mengqiao Cui Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice Communications Biology |
| title | Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| title_full | Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| title_fullStr | Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| title_full_unstemmed | Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| title_short | Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| title_sort | selective activation of sigmar1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice |
| url | https://doi.org/10.1038/s42003-025-07590-2 |
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