Abstract
Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson’s disease.
Highlights
Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, their role is still unclear
Much uncertainty still exists about the aetiology of Parkinson’s disease (PD), available evidence suggests the implication of numerous processes such as oxidative stress, mitochondrial dysfunction, inflammation and cell apoptosis
Samples from the four experimental groups were distinctly separated in the principal component analysis (PCA) plot, indicating a differential gene expression profile caused by both intoxications (Fig. 2c)
Summary
Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The deleterious role of systemic inflammation in the onset and progression of PD is becoming evident, so that the interest in its study has increased in the last years[1] In this sense, it is showed that dopaminergic neurons are more vulnerable to oxidative stress and pro-inflammatory cytokines because of their low levels of intracellular glutathione c oncentrations[2]. In our previous study, we showed an exacerbation of the dopaminergic neuronal death and the glial activation both in the SNpc and striatum when combining MPTP and DSS intoxications[8]
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