In microglia, inducible nitric oxide synthase can induce dopaminergic neurons to promote the intake of paraquat. However, exposure to paraquat can result in specific injury to dopaminergic neurons. The substantia nigra pars compacta in patients has activated microglia, but the role of oxidative stress injury is unkonwn.OBJECTIVE:
To explore the role of microglia mediated oxidative stress injury in mouse models of Parkinson's disease.METHODS:
Thirty-six C57BL/6 mice were randomly divided into two groups with 18 mice in each: Parkinson's disease group and control group. The model of Parkinson's disease was established by intraperitoneal injection of paraquat to mice (10 mg/kg). The control group was given the same dose of normal saline as paraquat. Adult spontaneous motor activity was observed in the two groups. The level of dopamine in the substantia nigra pars compacta was observed by high-performance liquid chromatography. The expressions of tyrosine hydroxylase and mac-1 in the substantia nigra pars compacta were measured by immunohistochemical staining under optical microscope. The spectrophotometry was used to detect the activities of glutathione, superoxide dismutase and glutathione peroxidase and the content of malondialdehyde in the substantia nigra pars compacta.RESULTS AND CONCLUSION:
Parkinson's disease group showed a marked hypoactive behavior and the number of microglia as compared with the control group (P < 0.05). Immunohistochemical staining showed tyrosine hydroxylase expression in the Parkinson's disease group was decreased, but mac-1 was increased compared with the control group (P < 0.05). The content of dopamine in the substantia nigra pars compacta was lower than that in the control group detected by high-performance liquid chromatography (P < 0.05). The activities of glutathione, superoxide dismutase, and glutathione peroxidase were significantly reduced in the Parkinson's disease group, but the content of malondialdehyde was increased as compared with the control group (P < 0.05). These findings indicate that activated microglia in the substantia nigra pars compacta can strengthen oxidative stress injury and weaken anti-oxidative protection, which may be an important pathogenesis of Parkinson's disease.RESULTS AND CONCLUSION:
Lu MJ, Wang SS, Zhu Y. Microglia-mediated oxidative stress injury in a mouse model of Parkinson's disease. Zhongguo Zuzhi Gongcheng Yanjiu. 2013;17(11): 2001-2006.