Hunter Randy, Ojha Uttam, Bhurtel Sunil, Bing Guoying, Choi Dong-Young
Department of Anatomy and Neurobiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Neurosci Res. 2017 Jan;114:62-69. doi: 10.1016/j.neures.2016.09.007. Epub 2016 Sep 22.
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.
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，炎症通过加剧氧化应激和线粒体功能障碍的恶性循环来介导神经元损伤。细菌内毒素脂多糖（LPS）可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丢失这一假说，我们将LPS或生理盐水注射到大鼠纹状体中。在此，我们发现纹状体内注射LPS会导致线粒体呼吸功能缺陷、线粒体嵴损伤、线粒体氧化和硝化。最后，我们发现LPS注射一周后黑质中多巴胺能神经元显著丢失。这项研究表明，LPS诱导的多巴胺能神经变性可能是由线粒体损伤所致。
