Stress inhibits tryptophan hydroxylase expression in a rat model of depression
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Yi Chen1,2,*, Haixia Xu1,2,*, Mingyue Zhu1,2, Kun Liu1,2, Bo Lin1,2, Ruxian Luo3, Chuanbai Chen3 and Mengsen Li1,2
1Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571199, Hainan Province, P. R. China
2Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, Hainan Province, P. R. China
3Department of Psychiatry, Hainan Provincial Anning Hospital, Haikou 571199, Hainan Province, P. R. China
*These authors have contributed equally to this work and are co-first authors
Mengsen Li, email: [email protected]
Chuanbai Chen, email: [email protected]
Keywords: depressive model, tryptophan hydroxylase, epigenetics
Received: March 14, 2017 Accepted: May 21, 2017 Published: June 28, 2017
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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