Experimental destruction of dopaminergic neurons initiated by lipopolysaccharide

Objective To investigate lipopolysaccharide(LPS)-induced injury of dopaminergic neurons in the substantia nigra and effect of LPS on animals behavior in vitro and in vivo. Methods Pheochromocytoma(PC12)cell viability was estimated by MTT assay after cells had been differently incubated in medium containing LPS, 6-OHDA and culture supernatant of LPS-treated microglia. LPS was stereotactically injected into left substantia nigra of rats. 14,21 and 28 days after injection, the circling behavior was observed by intraperitoneal injection of apomorphine. Midbrain dopaminergic neurons were identified by using tyrosine hydroxylase (TH) immunohistochemistry. The contents of dopamine and its metabolites in the striatum and substantia nigra were measured by high performance liquid chromatography(HPLC). Results LPS alone had no influence on cell viability. However, the 26% and 30% reduction of cell viability was found when cells were exposed to culture supernatant of LPS-treated microglia and 6-OHDA. The circling behavior ipsilateral to LPS-treated side was induced in some rats 21 and 28 days following injection, but not 14 days. Compared with the PBS-treated rats, the marked (35%~60%) loss of TH-positive cells in left substantia nigra was identified 21 and 28 days after LPS treatment, but not 14 days. The 30%~70% reduction of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in left striatum and substantia nigra was found at 21 and 28 days following injection, whereas no significant change was observed at 14 days. Conclusions LPS could indirectly injury the dopaminergic neurons and induce behavioral asymmetry of rats.