Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway
Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway
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DOI：
10.1016/j.neures.2016.09.007
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发表时间：
2017-01-01
影响因子：
2.9
通讯作者：
Choi, Dong-Young
中科院分区：
文献类型：
--
作者：
Hunter, Randy;Ojha, Uttam;Choi, Dong-Young
越来越多的证据表明，慢性炎症在帕金森病中发生的进行性多巴胺能神经变性中起作用。据推测，炎症介导的神经元损伤通过恶化的恶性循环的氧化应激和线粒体功能障碍。细菌内毒素脂多糖（LPS）诱导小胶质细胞活化和炎症驱动的多巴胺能神经变性。为了验证LPS诱导的炎症反应可能损害线粒体结构和功能导致黑质多巴胺能神经元损失的假设，我们将LPS或生理盐水注射到大鼠纹状体中。在这里，我们发现，纹状体内LPS诱导线粒体呼吸，线粒体嵴，线粒体氧化和硝化损伤的赤字。最后，我们发现注射LPS后一周，黑质多巴胺能神经元明显减少。本研究提示LPS诱导的多巴胺能神经元变性可能是通过线粒体损伤实现的。(C)2016爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Accumulating evidence.suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury. (C) 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.