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Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis

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.
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Submitted on : Monday, September 21, 2020 - 2:27:58 PM
Last modification on : Saturday, December 4, 2021 - 4:09:27 AM
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Ana-Luisa Gil-Martinez, Lorena Cuenca-Bermejo, Ana Maria Gonzalez-Cuello, Consuelo Sanchez-Rodrigo, Antonio Parrado, et al.. Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.13147. ⟨10.1038/s41598-020-69695-4⟩. ⟨inserm-02944403⟩



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