title: SIRT2 is involved in the modulation of depressive behaviors.
abstract: Exposure to chronic stress produces negative effects on mood and hippocampus-dependent memory formation. SIRT2 alteration has been reported in mood disorders; however, the role of SIRT2 in depression remains unclear. Therefore, we aimed to determine whether SIRT2 can restore stress-induced suppression of neurogenesis in a rat chronic unpredictable stress (CUS) model of depression. Sucrose preference test, home-cage locomotion, forced swim test, and elevated plus maze were used to determine the role of SIRT2 in CUS model. To further determine the hippocampal neurogenesis contributes to the role of SIRT in mediating the antidepressant-like behavior, rats were exposed to X-irradiation to disrupt the process of hippocampal neurogenesis. CUS decreased expression of the SIRT2 protein in the hippocampus. Treatment with the antidepressant fluoxetine reversed the CUS-induced SIRT2 change. Furthermore, inhibiting SIRT2 by tenovin-D3 resulted in depression-like behaviors and impaired hippocampal neurogenesis in rats. Conversely, overexpression of SIRT2 by the intra-hippocampal infusion of recombinant adenovirus vector expressing mouse SIRT2 reversed the CUS-induced depressive-like behaviors, and promoted neurogenesis. Disrupting neurogenesis in the dentate gyrus by X-irradiation abolished the antidepressant-like effect of Ad-SIRT2-GFP. These findings indicate that hippocampal SIRT2 is involved in the modulation of depressant-like behaviors, possibly by regulating neurogenesis.
authors: Department of Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Rui
authors: R
authors: Liu
authors: Department of Psychiatry, Xi'an Mental Health Center, Xi'an 710061, P.R. China.
authors: Wei
authors: W
authors: Dang
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Ying
authors: Y
authors: Du
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Qiong
authors: Q
authors: Zhou
authors: Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Kai
authors: K
authors: Jiao
authors: Department of Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Zhaohui
authors: Z
authors: Liu
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D003863:Depression / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D051381:Rats; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000813:Anilides; C583853:tenovin-D3; D056565:Sirtuin 2; D013890:Thiourea