Étude de la microglie chez les singes lésés au MPTP comme modèle de la maladie de Parkinson : effet du traitement à la lévodopa

Authors: Lecours, Cynthia
Advisor: Tremblay, Marie-Ève; Di Paolo, Thérèse; Parent, Martin
Abstract: Microglia are the brain immune cells which exert crucial physiological roles across the lifespan. To assess whether their functions are impaired in the pathophysiology of Parkinson disease (PD), the most common neurodegenerative motor disorder, we characterized their changes in density, morphology, ultrastructure, and degradation activity among the sensorimotor functional territory of the putamen, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cynomolgus monkeys. A subset of MPTP monkeys was also treated with oral levodopa (L-DOPA). These monkeys developed L-DOPA-induced dyskinesia (LID) similar to what PD patients experience after only five to ten years of treatment. Using light, confocal and electron microscopy, our results showed alterations of microglial density, morphology and function following MPTP intoxication that were partially normalized with L-DOPA treatment. Microglial density, cell body and arborization areas were increased in the PD monkeys, with these cells showing a more hyper-ramified morphology, whereas L-DOPA- treated animals presented a microglial phenotype similar to control animals. At the ultrastructural level, microglia appeared healthy, without dilation of the Golgi apparatus and endoplasmic reticulum, among other cellular stress markers,in MPTP monkeys. Nevertheless, microglia displayed a reduced number of phagocytic inclusions in the MPTP group, suggesting impaired degradation activity. Moreover, a decreased immunoreactivity for CD68 –a lysosome-associated glycoprotein– was measured in microglia from MPTP animals treated with L-DOPA. The subcellular localization of CD68 among secondary lysosomes and tertiary residual bodies was also confirmed in microglia by electron microscopy. Taken together, these findings revealed significant microglial phenotypic changes during PD pathophysiology that were partially rescued by L-DOPA treatment.
Document Type: Mémoire de maîtrise
Issue Date: 2019
Open Access Date: 15 February 2021
Permalink: http://hdl.handle.net/20.500.11794/68159
Grantor: Université Laval
Collection:Thèses et mémoires

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