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
Date
2022
Authors
Morissette, Marc
Bourque, Mélanie
Tremblay, Marie-Ève
Di Paolo, Thérèse
Journal Title
Journal ISSN
Volume Title
Publisher
Cells
Abstract
Proinflammatory 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.
Description
Keywords
inflammation, L-Dopa-induced dyskinesias, Parkinson, MPEP, L-Dopa, MPTP monkey, GFAP, Iba1, CD68, basal ganglia
Citation
Morissette, 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/cells11040691