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The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
Stress inhibits tryptophan hydroxylase expression in a rat model of depression
Yi Chen1,2, Haixia Xu1,2, Mingyue Zhu1,2
1Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571199, Hainan Province, P. R. China.
Abstract:
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats. Immunohistochemical analyses of TPH1/2 showed less TPH1 and TPH2 expression, specifically TPH2, in the brain, liver and kidney of the depressive rats than in the healthy rats; In addition, the two TPH isoforms, TPH1 and TPH2, had different spatial distributions,the mRNAs of the TPH1/2 genes were significantly decreased and TPH1/2 were highly methylated in the depressive model rat, but treatment with paroxetine ameliorated the expression and methylation of TPH1/2. All together, stress was able to inhibit expression of TPH1/2 in brain tissue and decrease concentration of 5-HT, the mechanism maybe involve in increasing the methylation of TPH2 genes promoter; Paroxetine has a role in confronting the effect of stress in depressive rat model.
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Repressible Operon: trp Operon

