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应激抑制抑郁症大鼠模型中色氨酸羟化酶的表达。

Stress inhibits tryptophan hydroxylase expression in a rat model of depression.

作者信息

Chen Yi, Xu Haixia, Zhu Mingyue, Liu Kun, Lin Bo, Luo Ruxian, Chen Chuanbai, Li Mengsen

机构信息

Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571199, Hainan Province, P. R. China.

Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, Hainan Province, P. R. China.

出版信息

Oncotarget. 2017 Jun 28;8(38):63247-63257. doi: 10.18632/oncotarget.18780. eCollection 2017 Sep 8.

DOI:10.18632/oncotarget.18780
PMID:28968985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5609917/
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 genes promoter; Paroxetine has a role in confronting the effect of stress in depressive rat model.

摘要

血清素（5-羟色胺，5-HT）功能障碍与抑郁症的病理生理学相关。色氨酸羟化酶（TPH）是5-HT生物合成中的限速酶，被认为在包括抑郁症在内的许多精神障碍中起重要作用。在本研究中，我们通过使动物遭受应激建立了抑郁症大鼠模型，然后用帕罗西汀对大鼠进行治疗。结果表明，抑郁症大鼠模型脑和肝组织中5-HT的浓度显著低于健康大鼠或接受治疗的大鼠。TPH1/2的免疫组织化学分析显示，与健康大鼠相比，抑郁大鼠脑、肝和肾中TPH1和TPH2的表达较少，尤其是TPH2；此外，两种TPH亚型TPH1和TPH2具有不同的空间分布，抑郁模型大鼠中TPH1/2基因的mRNA显著减少且TPH1/2高度甲基化，但帕罗西汀治疗改善了TPH1/2的表达和甲基化。总之，应激能够抑制脑组织中TPH1/2的表达并降低5-HT的浓度，其机制可能涉及增加基因启动子的甲基化；帕罗西汀在对抗抑郁大鼠模型中的应激作用方面具有一定作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/cd52ac89cdd0/oncotarget-08-63247-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/7139e78f1979/oncotarget-08-63247-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/70791916e601/oncotarget-08-63247-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/3cd16dbdea3a/oncotarget-08-63247-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/c3be7801f93c/oncotarget-08-63247-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/cd52ac89cdd0/oncotarget-08-63247-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/7139e78f1979/oncotarget-08-63247-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/70791916e601/oncotarget-08-63247-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/3cd16dbdea3a/oncotarget-08-63247-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/c3be7801f93c/oncotarget-08-63247-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b4/5609917/cd52ac89cdd0/oncotarget-08-63247-g005.jpg

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