Pro-inflammatory cytokines and their receptors expression in a mouse model of parkinson's like-disease

Upregulation of inflammatory response in the brain is associated with a number of neurodegenerative diseases, including Alzheimer‟s and Parkinson‟s disease (PD), amyotrophic lateral sclerosis, multiple sclerosis. In particular PD is a common neurodegenerative pathological state characterised by the degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta, determining reduced dopamine levels in the caudate-putamen (CP) which lead to movement malfunction. Despite intensive research, the cause of neuronal loss in PD is poorly understood. To study the specific cause of PD, researchers have used a variety of toxins as agents to bring about damage to the dopaminergic neurons, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat and rotenone. Among these, the MPTP poisoning leads to symptoms very closely matched to many features of Parkinsonian syndrome in both humans and animals. In this study we investigated, in an experimental MPTP mouse model of PD, the expression of pro-inflammatory cytokines interleukin (IL)-1 , tumor necrosis factor (TNF)- α and IL-6 and their receptors in the SN and CP, in order to evaluate their involvement in this neurodegenerative disease. In MPTP-treated animals we observed a significant increase in IL-1 , TNF- α and IL-6 mRNA expression levels both in the SN and CP in comparison with untreated mice. In addition, both mRNA and protein levels of IL-1RI, TNF- α RI and IL-6R were significantly enhanced in the SN of MPTP-treated mice in comparison to controls, whereas no significant differences were observed in the CP between treated and untreated mice. Overall, these results indicate a possible role of both pro-inflammatory cytokines and their receptors in the pathogenesis of PD.