Long-term effect of intraventricular injection of low-dose lipopolysaccharide on behavior, microglias and dopaminergic neurons in the substantia nigra of rats

Abstract

Objective To investigate the long-term effect of inflammation on behavior,microglias and dopaminergic （DA） neurons in the substantia nigra of intracephalic inflammation rat models induced by intracerebroventricular injection of low-dose（10μg） lipopolysaccharide （LPS）. To analyze the relationship between activa- tion of microglias and DA neurons degeneration in order to explore the mechanism of inflammation in the progres- sive process of Parkinson＇s disease （PD）. Methods 50 healthy male SD rats were randomly assigned into sa- line-injected control group and 10μg LPS-injected group. All injections were made intracerebroventricularly on right side of rats with saline or LPS. Moving speed was measured at different time points. At 24 weeks and 40 weeks after saline or LPS injection, specific antibodies of OX-42 and OX-6 were used separately to detect the changes of microglia in the substantia nigra of rat. The changes in morphology and numbers of substantia nigra DA neurons were observed by tyrosine hydroxylase（TH） immunohistochemical staining. The expression and distribution of the degenerated neurons in substantia nigra were detected by using Fluoro-Jade B （FJB）. Results （1）Analysis of moving speed showed that the moving speed of 10μg LPS-injected group rats and saline-injected group rats was similar from 4 weeks to 36 weeks after injection. At 40 weeks post injection, moving speed of 10μg LPS-injected group rats decreased by 24.6% compared with that of saline-injected group rats （P〉 0.05 ）. （2）At 24 weeks and 40 weeks after injection,there were many activated 0X-42 positive microglias in the substantia nigra of 10μg LPS-in- jected group rats, but there was almost no significant activated OX-42 positive microglia in saline-injected group. OX-6 positive microglias were not found in the substantia nigra of both of two groups. （1）At 24 weeks and 40 weeks post injection, the number of TH-positive neurons in the substantia nigra of 10μg LPS-iniected rout3 rats decreasedby 24.2% （ t=4.803, P〈0.01 ） and 27.6% （ t= 3. 212, P〈0.01 ） respectively compared with those of salineinjected group. （4） There was no FJB positive neurons in the suhstantia nigra of the two group rats. Conclusion Intraventricular injection of low-dose LPS （10μg） in rats may induce long-term activation of microglias and chronic degeneration of DA neurons in the substantia nigra of rats although the necrosis are not occurs to DA neurons till 40 weeks post LPS injection. Intravenlricular injection of low-dose LPS in rats could he ideal model to study the mechanism of chronic degeneration of DA neurons in PD. Key words: Parkinson＇ s disease ; Inflammation ; Behaviour ; Microglia ; Dopaminergic neurons