Upregulation of microglial C1q expression has no effects on nigrostriatal dopaminergic injury in the MPTP mouse model of Parkinson disease.

Abstract

Here we analyzed C1q, the initial recognition subcomponent of classical complement activation cascade, in an experimental model of Parkinson disease (PD). Nigrostriatal dopaminergic pathway injury was induced by treatment of wildtype mice subchronically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Constitutive expression of C1q was restricted to microglia throughout the brain, and microglial C1q expression was early and transiently upregulated after MPTP in the substantia nigra (SN) and striatum, as analyzed by immunohistochemistry and in situ hybridization. C1q-positive microglia exhibited morphological characteristics of activated macrophage-type of cells, co-stained for MHCII, proliferated and were in close contact with degenerating dopaminergic neurons and fibers in the MPTP-lesioned SN. However, mice deficient in functional C1q protein were not significantly different in MPTP-induced loss of nigral dopaminergic neurons, striatal dopaminergic fibers and dopamine levels than their control littermates. In conclusion, C1q is upregulated and considered to be a marker of microglial activation in the nigrostriatal system after subchronic MPTP, but nigrostriatal dopaminergic injury may be not affected by C1q in this model.