Expression of TLR4 and CD14 in the Central Nervous System (CNS) in a MPTP Mouse Model of Parkinson's-Like Disease

Systemic infections are often associated with neurodegenerative processes in many diseases of the central nervous system (CNS), including Parkinson's disease. Toll-like receptor (TLR)4 and CD14 act as receptors for lipopolysaccharide (LPS) released by gram-negative bacteria. In this contest, CD14 functions as the main LPS ligand and TLR4 transmits the LPS signal into the cell. In this paper, we investigated the expression of TLR4 and CD14, in different anatomical areas of the CNS, in an experimental model of Parkinson's-like disease, represented by MPTP-treated mouse. In particular, we analyzed the gene transcripts and proteins expression of CD14 and TLR4, in the substantia nigra and caudate-putamen nuclei of these animals. Results demonstrated an augmented expression of both CD14 and TLR4 in the substantia nigra of mice treated with MPTP in comparison to untreated animals, suggesting that the endotoxin receptors are over expressed in different manner in specific areas of the CNS during Parkinson's-like disease

MPTP-Induced Neuroinflammation Increases the Expression of Pro-Inflammatory Cytokines and Their Receptors in Mouse Brain

Parkinson's disease (PD) is a common neurodegenerative disease characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Despite intensive research, the cause of neuronal loss in PD is poorly understood. Inflammatory mechanisms have been implicated in the pathophysiology of PD. In this study, conducted on an experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, we investigated the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and their receptors (IL-1RI, TNF-αRI, IL-6Rα) at the SN and caudate-putamen (CP) levels. In MPTP-treated animals we observed a significant increase in IL-1β, 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-αRI and IL-6Rα 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 role of both pro-inflammatory cytokines and their receptors in the pathogenesis of PD

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