Study on Lipopolysaccharide Injury of Dopaminergic Neurons and Its Relevant Mechanism

Objective To study lipopolysaccharide (LPS)-induced injury of dopaminergic neurons and the relevant immunity and the pathogenesis of Parkinson disease (PD).Methods Lipopolysaccharide was stereostatically injected into unilateral substantia nigra of rats.The circling behavior was observed by intraperitoneal-injection of apomorphine during the intervals of 2,3 and 4 weeks after injection.The contents of monoamine in the nigrostriatal system were measured by high performance liquid chromatography (HPLC).Tyrosine hydroxylase (TH)immunohistochemistry was used to detect midbrain dopaminergic neurons. Nissl staining indirectly indicated the activation of microglia, and at the same time the synthesis of inducible nitric oxide (iNOS) were identified by double immunity enzyme staining. Results The circling behavior ipsilateral to LPS injected-side was induced in some rats 3 and 4 weeks following injection, but not in 2 weeks. Compared with the control rats, the 30%-70% reduction of dopamine and its metabolite (DOPAC) in the lesion of striatum and substantia nigra was found at 2 ,3 and 4 weeks time groups.The marked loss of TH-positive cells in the injured substantia nigra was identified,especially 3 and 4 weeks after LPS treatment. The activation of microglia and synthesis of iNOS were also observed by Nissl staining and double immunity enzyme staining.Conclusions LPS intranigral injection could injure the dopaminergic neurons in the substantia nigra.Both activation of microglia and release of NO played an important role in the death of the neurons. Thus, it suggests that immunity may be involved in the pathogenesis of PD.