Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson's disease.
Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson's disease.
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DOI：
10.1016/j.bbi.2015.08.015
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Kakinuma Y
中科院分区：
文献类型：
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作者：
Sugama S;Sekiyama K;Kodama T;Takamatsu Y;Takenouchi T;Hashimoto M;Bruno C;Kakinuma Y
帕金森病（Parkinson's disease，PD）是一种神经退行性疾病，其特征是黑质（substantia nigra pars rectuata，SNpc）多巴胺能（dopaminergic，DA）神经元的缺失，蓝斑（locus coeruleus，LC）去甲肾上腺素能神经元的缺失程度较轻。大多数PD病例是特发性和散发性的，被认为是环境和遗传因素的结果。在这里，据我们所知，我们报告的第一个证据表明，慢性束缚应激（8小时/天，5天/周）大大减少黑质DA和LC去甲肾上腺素能神经元细胞的数量在大鼠。DA神经元在SNPC的损失是明显的2周后的压力和进展的时间依赖性的方式，在16周达到61%。这种减少伴随着强大的小胶质细胞活化和氧化应激，并在中脑的SNpc和LC中以硝基酪氨酸为标志。这些结果表明，慢性应激触发DA和去甲肾上腺素能神经退行性变，通过增加氧化应激，并在黑质和LC中激活的小胶质细胞可能发挥重要作用，在调节氧化应激的神经毒性作用。总之，这些数据表明，暴露于慢性应激触发DA和去甲肾上腺素能神经变性，这是PD的原因。
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and, to a lesser extent, in the noradrenergic neurons of the locus coeruleus (LC). Most cases of PD are idiopathic and sporadic and are believed to be the result of both environmental and genetic factors. Here, to the best of our knowledge, we report the first evidence that chronic restraint stress (8 h/day, 5 days/week) substantially reduces nigral DA and LC noradrenergic neuronal cell numbers in rats. Loss of DA neurons in the SNpc was evident after 2 weeks of stress and progressed in a time-dependent manner, reaching up to 61% at 16 weeks. This reduction was accompanied by robust microglial activation and oxidative stress and was marked by nitrotyrosine in the SNpc and LC of the midbrain. These results indicate that chronic stress triggers DA and noradrenergic neurodegeneration by increasing oxidative stress, and that activated microglia in the substantia nigra and LC may play an important role in modulating the neurotoxic effects of oxidative stress. Taken together, these data suggest that exposure to chronic stress triggers DA and noradrenergic neurodegeneration, which is a cause of PD.