Prevention of L-Dopa-induced dyskinesias by MPEP blockade of metabotropic glutamate receptor 5 is associated with reduced inflammation in the brain of Parkinsonian monkeys

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dc.contributor.authorMorissette, Marc
dc.contributor.authorBourque, Mélanie
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorDi Paolo, Thérèse
dc.date.accessioned2022-10-27T19:46:56Z
dc.date.available2022-10-27T19:46:56Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.description.abstractProinflammatory markers were found in brains of Parkinson’s disease (PD) patients. After years of L-Dopa symptomatic treatment, most PD patients develop dyskinesias. The relationship between inflammation and L-Dopa-induced dyskinesias (LID) is still unclear. We previously reported that MPEP (a metabotropic glutamate receptor 5 antagonist) reduced the development of LID in de novo MPTP-lesioned monkeys. We thus investigated if MPEP reduced the brain inflammatory response in these MPTP-lesioned monkeys and the relationship to LID. The panmacrophage/microglia marker Iba1, the phagocytosis-related receptor CD68, and the astroglial protein GFAP were measured by Western blots. The L-Dopa-treated dyskinetic MPTP monkeys had increased Iba1 content in the putamen, substantia nigra, and globus pallidus, which was prevented by MPEP cotreatment; similar findings were observed for CD68 contents in the putamen and globus pallidus. There was a strong positive correlation between dyskinesia scores and microglial markers in these regions. GFAP contents were elevated in MPTP + L-Dopa-treated monkeys among these brain regions and prevented by MPEP in the putamen and subthalamic nucleus. In conclusion, these results showed increased inflammatory markers in the basal ganglia associated with LID and revealed that MPEP inhibition of glutamate activity reduced LID and levels of inflammatory markers.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by a grant from the Canadian Institutes of Health Research (CIHR) (#341846). MET is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition.en_US
dc.identifier.citationMorissette, M., Bourque, M., Tremblay, M., & Di Paolo, T. (2022). “Prevention of LDopa-induced dyskinesias by MPEP blockade of metabotropic glutamate receptor 5 is associated with reduced inflammation in the brain of Parkinsonian monkeys.” Cells, 11(4), 691. https://doi.org/10.3390/cells11040691en_US
dc.identifier.urihttps://doi.org/10.3390/cells11040691
dc.identifier.urihttp://hdl.handle.net/1828/14345
dc.language.isoenen_US
dc.publisherCellsen_US
dc.subjectinflammationen_US
dc.subjectL-Dopa-induced dyskinesiasen_US
dc.subjectParkinsonen_US
dc.subjectMPEPen_US
dc.subjectL-Dopaen_US
dc.subjectMPTP monkeyen_US
dc.subjectGFAPen_US
dc.subjectIba1en_US
dc.subjectCD68en_US
dc.subjectbasal gangliaen_US
dc.titlePrevention of L-Dopa-induced dyskinesias by MPEP blockade of metabotropic glutamate receptor 5 is associated with reduced inflammation in the brain of Parkinsonian monkeysen_US
dc.typeArticleen_US

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