Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline

Abstract

Levo-dihydroxyphenylalanine (L-DOPA) therapy for Parkinson's disease (PD) patients improves motor symptoms, but long-term treatment induces side effects such as abnormal involuntary movements (levodopa-induced dyskinesia – LID). Increasing evidence has linked LID with neuroinflammatory reaction in the striatum involving microglia and astrocytes. The nerve/glial antigen-2 cells (NG2-glia) are recognized as a glial cell whose function in the adult brain is poorly understood. Here, we used immunohistochemistry, confocal microscopy, and western blot to characterize the cellular distribution of NG2-glia in the dorsal striatum of unilaterally 6OHDA-lesioned rats presenting LID. The effect of doxycycline on NG2-glia cells was determined. Dopamine depletion revealed a minor density increase of NG2-glia in the dorsolateral striatum and an activated phenotype. LID development promotes a decrease in NG2-glia cell density and protein level, maintaining the cell-activated feature. Doxycycline antidyskinetic therapy restores the cells to the control density profile. These results indicated the cellular distribution of NG2-glia in the striatum, but the interaction between these cells and other glial types in this model was unanswered and therefore we carried out a double labeling of NG2 and OX-42 (microglia) and GFAP (astrocyte). In LID, there was a decrease in the possible NG2 and OX-42 positive cells interaction, with no effect in the astrocytes. Doxycycline treatment restored the control characteristic. The ability of NG2-glia to regulate their dynamics in response to PD and LID is the first indication of an active link between them. The results suggest that NG2 cells may play important roles other than serving as oligodendrocyte precursor cells. Summary Statement NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.