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However, how the levels of a single EAA affects depressive behaviors remains elusive. Here, we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice, it remarkably reverses the depression-like behaviors induced by chronic restraint stress (CRS). This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs. Furthermore, the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol. Moreover, hypothalamic agouti-related peptide (AgRP) neural activity changes during CRS and leucine deprivation, and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation. Finally, the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2 (GCN2) in AgRP neurons. Taken together, our results suggest a new drug target and\/or dietary intervention for the reduction of depressive symptoms.<\/jats:p>","DOI":"10.1093\/lifemeta\/load004","type":"journal-article","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T14:10:15Z","timestamp":1675519815000},"source":"Crossref","is-referenced-by-count":15,"title":["Leucine deprivation results in antidepressant effects via GCN2 in AgRP neurons"],"prefix":"10.1093","volume":"2","author":[{"given":"Feixiang","family":"Yuan","sequence":"first","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200032 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangming","family":"Wu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai 200031 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai 200031 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuxin","family":"Jiao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, 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