Nigrostriatal inflammation is associated with nonmotor symptoms in an experimental model of prodromal Parkinson’s disease

Abstract

Abstract Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson’s disease (PD). However, it is unclear whether the immune changes are involved in the initial physiopathology of PD, leading to the non-motor symptoms (NMS) observed in the prodromal PD stage. The current study aimed to characterize the behavioral and cognitive changes in a toxic-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal (i.n.) infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons. In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxious-like behaviors, but did not influence motor function. In addition, iba-1 and GFAP expressions were increased in the SNpc, suggesting an activated state of microglia and astrocytes. Consistent with this finding, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and tropomyosin receptor kinase (Trk) A mRNA in the SNpc. The striatum showed increased IL-17A and decreased BDNF and NFG levels compared to control mice. In conclusion, our results suggest that neuroinflammation may play an important role in the early stage of experimental PD-like syndrome. Our data also indicate that i.n. administration of MPTP may represents a valuable mouse model for prodromal PD.