Effects of Nigral Lipopolysaccharide Administration on Dopaminergic neural Dysfunction and Glial Cell Activation

Objective:To investigate the effects of nigral lipopolysaccharide (LPS) administration on dopaminergic neural dysfunction and glial cell activation. Methods:Sixty female SD rats were randomly divided into 5 groups: control, 1-day, 1-week, 2-week and 2-month. LPS was stereostatically injected into unilateral substantia nigra of rats except control group. At different survival time points, circling behavior was observed by intraperitoneal injection of Apo morphine during the intervals of 1 week to 2 months after injection. The damage to the substantia nigra DA neurons was observed by tyrosine-hydroxylase (TH) immunohistochemical staining. Specific antibody OX-42 was used to detect the changes in morphology and the number of microglia. Immunohistochemistry was used to detect midbrain dopaminergic neurons and microglia. The contents of monoamine in the nigrostriatal system were measured by high performance liquid chromatography (HPLC). The degenerative neurons in the substantia nigra were detected by Fluoro-JadeB staining. Results:Compared with the control group, the 12% to 71.5% reduction of TH-positive cells in the lesion of substantia nigra was found in 1-day, 1-week, 2-week and 2-month groups after LPS treatment. Compared with the control group, the 28.2%-65.7% reduction of dopamine and its metabolite (DOPAC) in the lesion of striatum and substantia nigra was found in 1-day, 1-week, 2-week and 2-month groups. The activation of microglia was also observed from 24 h to 2 months after LPS treatment. There were a number of the positive degenerative neurons in the substantia nigra. Conclusion:LPS intranigral injection could induce the activation of microglia and the degeneration of dopaminergic neurons in the substantia nigra.