Tet2 acts in the lateral habenula to regulate social preference in mice
Summary: The lateral habenula (LHb) has been considered a moderator of social behaviors. However, it remains unknown how LHb regulates social interaction. Here, we show that the hydroxymethylase Tet2 is highly expressed in the LHb. Tet2 conditional knockout (cKO) mice exhibit impaired social prefere...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723007064 |
| _version_ | 1797788485145329664 |
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| author | Xingyun Xu Hang Zhou Hainan Wu Zhigang Miao Bo Wan Haigang Ren Wei Ge Guanghui Wang Xingshun Xu |
| author_facet | Xingyun Xu Hang Zhou Hainan Wu Zhigang Miao Bo Wan Haigang Ren Wei Ge Guanghui Wang Xingshun Xu |
| author_sort | Xingyun Xu |
| collection | DOAJ |
| description | Summary: The lateral habenula (LHb) has been considered a moderator of social behaviors. However, it remains unknown how LHb regulates social interaction. Here, we show that the hydroxymethylase Tet2 is highly expressed in the LHb. Tet2 conditional knockout (cKO) mice exhibit impaired social preference; however, replenishing Tet2 in the LHb rescues social preference impairment in Tet2 cKO mice. Tet2 cKO alters DNA hydroxymethylation (5hmC) modifications in genes that are related to neuronal functions, as is confirmed by miniature two-photon microscopy data. Further, Tet2 knockdown in the glutamatergic neurons of LHb causes impaired social behaviors, but the inhibition of glutamatergic excitability restores social preference. Mechanistically, we identify that Tet2 deficiency reduces 5hmC modifications on the Sh3rf2 promoter and Sh3rf2 mRNA expression. Interestingly, Sh3rf2 overexpression in the LHb rescues social preference in Tet2 cKO mice. Therefore, Tet2 in the LHb may be a potential therapeutic target for social behavior deficit-related disorders such as autism. |
| first_indexed | 2024-03-13T01:36:13Z |
| format | Article |
| id | doaj.art-c622b6a5b90c4bbab97882b5ad9d80d0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T01:36:13Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c622b6a5b90c4bbab97882b5ad9d80d02023-07-04T05:09:53ZengElsevierCell Reports2211-12472023-07-01427112695Tet2 acts in the lateral habenula to regulate social preference in miceXingyun Xu0Hang Zhou1Hainan Wu2Zhigang Miao3Bo Wan4Haigang Ren5Wei Ge6Guanghui Wang7Xingshun Xu8Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou 215000, China; Institute of Neuroscience, Soochow University, Suzhou 215123, ChinaInstitute of Neuroscience, Soochow University, Suzhou 215123, China; PKU-Nanjing Joint Institute of Translational Medicine, Nanjing 211800, ChinaInstitute of Neuroscience, Soochow University, Suzhou 215123, ChinaInstitute of Neuroscience, Soochow University, Suzhou 215123, ChinaInstitute of Neuroscience, Soochow University, Suzhou 215123, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou 215123, ChinaDepartment of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221600, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China; Corresponding authorDepartment of Neurology, the First Affiliated Hospital of Soochow University, Suzhou 215000, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China; Corresponding authorSummary: The lateral habenula (LHb) has been considered a moderator of social behaviors. However, it remains unknown how LHb regulates social interaction. Here, we show that the hydroxymethylase Tet2 is highly expressed in the LHb. Tet2 conditional knockout (cKO) mice exhibit impaired social preference; however, replenishing Tet2 in the LHb rescues social preference impairment in Tet2 cKO mice. Tet2 cKO alters DNA hydroxymethylation (5hmC) modifications in genes that are related to neuronal functions, as is confirmed by miniature two-photon microscopy data. Further, Tet2 knockdown in the glutamatergic neurons of LHb causes impaired social behaviors, but the inhibition of glutamatergic excitability restores social preference. Mechanistically, we identify that Tet2 deficiency reduces 5hmC modifications on the Sh3rf2 promoter and Sh3rf2 mRNA expression. Interestingly, Sh3rf2 overexpression in the LHb rescues social preference in Tet2 cKO mice. Therefore, Tet2 in the LHb may be a potential therapeutic target for social behavior deficit-related disorders such as autism.http://www.sciencedirect.com/science/article/pii/S2211124723007064CP: Neuroscience |
| spellingShingle | Xingyun Xu Hang Zhou Hainan Wu Zhigang Miao Bo Wan Haigang Ren Wei Ge Guanghui Wang Xingshun Xu Tet2 acts in the lateral habenula to regulate social preference in mice Cell Reports CP: Neuroscience |
| title | Tet2 acts in the lateral habenula to regulate social preference in mice |
| title_full | Tet2 acts in the lateral habenula to regulate social preference in mice |
| title_fullStr | Tet2 acts in the lateral habenula to regulate social preference in mice |
| title_full_unstemmed | Tet2 acts in the lateral habenula to regulate social preference in mice |
| title_short | Tet2 acts in the lateral habenula to regulate social preference in mice |
| title_sort | tet2 acts in the lateral habenula to regulate social preference in mice |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723007064 |
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