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SIRT1 is a NAD+\u2010dependent class III histone deacetylase, widely expresses in BLA. However, epigenetic mechanisms in the BLA under the regulation of SIRT1 in the depression are largely uncharacterized. Under the chronic unpredictable chronic mild stress (CUMS) mouse model, we used adeno\u2010associated viral vectors (AAV) that encoded SIRT1\u2010shRNA or SIRT1 to specifically knockdown or overexpress SIRT1 in BLA neurons, respectively. CUMS procedure induced significant depression symptoms including the decreased sucrose preference, the less bodyweight gained, the decreased immobile latency and the increased immobile time both in forced swim test (FST) and tail suspension test (TST). Knockdown of SIRT1 in BLA glutamatergic neurons reversed these depression\u2010like behaviors and restored the synaptic abnormalities. Overexpression of SIRT1 in BLA glutamatergic neurons induced depression\u2010like behaviors in non\u2010stressed control mice. The result of protein expressions and ultrastructural changes were consistent with the behavioral results. Our study suggested that downregulation of SIRT1 in BLA has certain beneficial effect on CUMS\u2010induced depression\u2010like behaviors such as anorexia, anhedonia, hopelessness and despair. In addition, the increased expression of SIRT1 may be the immediate cause of depressive\u2010like symptoms. The abnormal expression of SIRT1 may affect the transcriptional regulation mechanism and signaling protein acetylation, affecting neuroplasticity and ultimately contribute to MDD. In the stress\u2010susceptible mice, these two mechanisms may co\u2010exist, but the specific mechanism needs further research.<\/jats:p>","DOI":"10.1111\/gbb.12765","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T06:38:39Z","timestamp":1628231919000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The role of <scp>SIRT1<\/scp> in the basolateral amygdala in depression\u2010like behaviors in mice"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-767X","authenticated-orcid":false,"given":"Hao","family":"Guo","sequence":"first","affiliation":[{"name":"College of Forensic Science Xi'an Jiaotong University  Shaanxi China"},{"name":"School of Sports Medicine and Rehabilitation Beijing Sport University  Beijing 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