title: Enhancing tyrosine hydroxylase and tryptophan hydroxylase expression and improving oxidative stress involved in the antidepressant effect of sodium valproate on rats undergoing chronic unpredicted stress.
abstract: Depression is a common worldwide mental disorder whose etiology remains unclear; there is also a lack of effective therapeutic agents. Sodium valproate (VPA) is a traditional antiepileptic drug with mood-stabilization effect and is increasingly being used to treat bipolar disorders and depression, but its antidepressant mechanism remains unknown. The aim of the present study was to investigate the possible mechanisms of antidepressant action by studying malondialdehyde level, catalase, and superoxide dismutase activities in the serum and the mRNA and protein expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in the prefrontal cortex of rats exposed to chronic unpredicted stress (CUS). Male Sprague-Dawley rats were used to establish a depression model by CUS. VPA (300 mg/kg once daily) and an equivalent volume of vehicle were administered to rats by an intragastric gavage. Rat behaviors, serum malondialdehyde level, serum catalase and superoxide dismutase activities, and the mRNA and protein expressions of TH and TPH in the prefrontal cortex were determined. The results showed that VPA treatment led to a significant decrease in depression-like behaviors, improvement in oxidative stress imbalance, and enhancement of TH, TPH mRNA, and protein expression in stressed rats, but failed to show any significant changes in control rats. This could indicate that the antidepressant mechanism of VPA is perhaps linked to upregulation of TH and TPH expression and inhibition of oxidative damage in CUS rats.
authors.affiliation: Departments of aPharmacology bDrug Analysis, Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy of Chongqing Medical University, Chongqing, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Qiu
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Yang
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Jiang
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D002374:Catalase / Q000097:blood; D003863:Depression / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000097:blood; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D000928:Antidepressive Agents; D012333:RNA, Messenger; D008315:Malondialdehyde; D014635:Valproic Acid; D002374:Catalase; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D013482:Superoxide Dismutase