title: Continuous GSK-3β overexpression in the hippocampal dentate gyrus induces prodepressant-like effects and increases sensitivity to chronic mild stress in mice.
abstract: BACKGROUND
  Glycogen synthase kinase-3 (GSK-3) has been linked to prodepressant-like effects in rodents. However, the roles of GSK-3β and the hippocampal dentate gyrus in regulating these behavioral effects remain unclear.
  
  
  METHODS
  A lentiviral vector was utilized to site-specifically express GSK-3β constitutively in the hippocampal DG in a mouse model of CMS. We examine the forced swim, tail suspension and the sucrose intake test. Acute and chronic administrations were conducted by dissolving fluoxetine hydrochloride (10ml/kg). We examine behavior tests as before, cellular apoptosis, proliferation and differentiation in the hippocampus.
  
  
  RESULTS
  GSK-3β expression levels persistently and significantly increased in the hippocampus following lenti-GSK-3β injections. In mice previously exposed to CMS, pre-injection of lentivirus-expressing GSK-3β into the hippocampal dentate gyrus significantly decreased sucrose preferences in the sucrose intake test and increased immobility times in both forced swim and tail suspension tests. In addition, fluoxetine resulted in similar antidepressant-like effects following chronic, but not acute, administrations under the same experimental conditions. Cellular apoptosis was observed in the hippocampal DG using TUNEL, revealing many TUNEL-positive cells in the lenti-GSK-3β mice. There were no significant changes in proliferation and differentiation.
  
  
  CONCLUSIONS
  We did not measure more biomarkers which were regulated by GSK-3β.
  
  
  CONCLUSIONS
  Results from this study demonstrated that site-specific injection of a lentivirus induced continuous GSK-3β expression in the hippocampal dentate gyrus of mice, resulting in prodepressant-like effects and increased sensitivity to chronic mild stress. Furthermore, chronic fluoxetine administration reversed these prodepressant-like effects and decreased neuronal apoptosis in the hippocampal DG in GSK-3β-overexpressing mice.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China. krzhang_sxmu@vip.163.com
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Xinrong
authors.initials: X
authors.lastname: Li
authors.forename: Pozi
authors.initials: P
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhongchen
authors.initials: Z
authors.lastname: Xie
authors.forename: Jvyi
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000378:metabolism*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D016086:Lentivirus; D008297:Male; D051379:Mice; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3