Age-associated myelin decompaction and CNPase expression differ in magnitude in the substantia nigra of MPTP-sensitive C57BL/6J mice and MPTP-resistant CD-1 mice

Abstract

Abstract Opposing phenomena of both oligodendrogliosis and oligodendroglial degeneration is reported in the striatum of MPTP-injected mice model of Parkinson’s disease (PD); reducing the clarity on their contribution to PD pathology. Furthermore, the role of oligodendroglia of substantia nigra pars compacta (SNpc), in pathogenesis and differential susceptibility to PD, is not known. In our earlier study, the MPTP-sensitive young C57BL/6J showed loss of 50-60% of SNpc neurons following MPTP, whereas the MPTP-resistant CD-1 showed a loss of 15-17%, suggesting better neuroprotection in the latter. We now investigate the effects of age and MPTP on oligodendroglial and myelin sheath ultrastructure, in SNpc, by electron microscopy as well as myelin-associated protein CNPase by semi-quantitative confocal microscopy and immunoblotting. MPTP-induced mitochondrial shrinkage suggests toxicity to mitochondria and dilation of Golgi-complex saccules indicates protein packaging deficits, in the oligodendroglia of young C57BL/6J. Contrariwise in CD-1, presence of elongated mitochondria and multiple polyribosomes may suggest preserved ultrastructure. The organelles were affected at middle age in C57BL/6J but at old age in CD-1. The neuropil of SNpc in both strains harbored unmyelinated and lightly myelinated fibers. The enhanced density of myelin fibers following MPTP, suggests re-myelination of surviving neurons. MPTP aggravated myelin decompaction at middle age in C57BL/6J, but at old age in CD-1. Upregulation of CNPase in MPTP-injected middle-aged CD-1 suggests attempt at compensation. Thus, oligodendroglia of the MPTP-sensitive strain shows degenerative features, while those of MPTP-resistant strain show compensatory capabilities against neuroinflammatory milieu; till middle age. It is pertinent to reconsider oligodendroglial involvement in PD.