Desipramine induced changes in the norepinephrine transporter, alpha- and gamma-synuclein in the hippocampus, amygdala and striatum.
Desipramine induced changes in the norepinephrine transporter, alpha- and gamma-synuclein in the hippocampus, amygdala and striatum.
复制标题
地昔帕明诱导海马、杏仁核和纹状体中去甲肾上腺素转运蛋白、α-和γ-突触核蛋白的变化。
DOI：
10.1016/j.neulet.2009.10.010
复制
发表时间：
2009
影响因子：
2.5
通讯作者：
Sidhu,Anita
中科院分区：
文献类型：
--
作者：
Jeannotte,AlexisM;McCarthy,JohnG;Sidhu,Anita
帕金森病（PD）抑郁症的高发病率已在临床上得到充分的证明，然而，这些重叠的病理的潜在分子机制仍然难以捉摸。使用啮齿动物抑郁症模型，Wistar-Kyoto（WKY）大鼠，我们以前证明，在额叶皮层中，α-和γ-突触核蛋白（α-Syn，γ-Syn）的表达和蛋白质相互作用的改变与去甲肾上腺素转运蛋白（NET）的异常运输有关。地昔帕明（Desipramine，DSI）是一种选择性NET抗抑郁药，长期治疗可导致抑郁样行为消失，并伴有α-Syn和γ-Syn表达及其NET转运的变化。使用相同的模型，我们检测了NET、α-Syn和γ-Syn在海马、杏仁核、脑干和纹状体中的表达，所有这些区域都与抑郁症或PD病理的发展或维持有关。在长期使用NTA治疗后，我们观察到海马、杏仁核和脑干中的NET显著降低;海马和杏仁核中的γ-Syn降低;海马和杏仁核中的α-Syn增加。出乎意料的是，我们观察到慢性多巴胺治疗后WKY纹状体中α-Syn表达显著降低。NET、α-Syn和γ-Syn在不同脑中表达的改变表明，α-Syn和γ-Syn对NET调节的区域特异性变化与RNP改善啮齿动物抑郁样行为的能力有关。
The high incidence of depression in Parkinson's disease (PD) has been well documented in the clinic; however, the underlying molecular mechanisms of these overlapping pathologies remain elusive. Using a rodent model of depression, the Wistar-Kyoto (WKY) rat, we previously demonstrated that in the frontal cortex the altered expression and protein interactions of α- and γ-synuclein (α-Syn, γ-Syn) were associated with dysregulated trafficking of the norepinephrine transporter (NET). Chronic treatment with desipramine (DMI), a NET-selective antidepressant, caused a disappearance of depressive-like behavior that was accompanied by a change in α-Syn and γ-Syn expression and their trafficking of NET. Using this same model, we examined the expression of NET, α-Syn and γ-Syn in the hippocampus, amygdale, brainstem, and striatum, all regions implicated in the development or maintenance of depression or PD pathology. Following chronic treatment with DMI, we observed a significant decrease in NET in the hippocampus, amygdala, and brainstem; decrease in γ-Syn in the hippocampus and amygdala; and, increase in α-Syn in the hippocampus and amygdala. Unexpectedly, we observed a significant decrease in α-Syn expression in the striatum of the WKY following chronic DMI treatment. The altered expression of NET, α-Syn and γ-Syn in different brain suggest that DMI's ability to improve depressive-like behavior in a rodent is associated with region-specific changes in the regulation of NET by α- and γ-Syn.