ABSTRACT
Glia show region-specific distribution in CNS and often mal-adapt to age-associated alterations in their niche. Some studies on autopsied nigra of Parkinson’s disease (PD) patients and experimental models propose gliosis as a putative trigger of neuronal loss. Epidemiological studies propose an ethnic bias in PD prevalence, as Caucasians are more susceptible than non-whites. Similarly, different mice strains are variably sensitive to MPTP. We had earlier likened divergent MPTP-sensitivity of C57BL/6J and CD-1 mice with differential susceptibility to PD based on differences in neuronal numbers.
Here we examined whether the variability was also incumbent to inter-strain differences in glial features. Stereological counts showed more microglia and fewer astrocytes in the nigra of MPTP-susceptible normal C57BL/6J mice, suggesting persistence of an immune-vigilant state. Pronounced MPTP-induced microgliosis and astrogliosis in both strains suggest glial involvement in pathogenesis. ELISA-based estimation of pro-inflammatory cytokines in the ventral midbrain revealed middle-age specific augmentation of TNF-α and IL-6 that reduced at old-age, suggesting middle-age as a critical, inflamm-aging associated time-point. IL-1β levels declined gradually. Inter-strain differences in TNF-α, including that seen post-MPTP, persisted across ageing while IL-6 and IL-1β showed upregulation at old-age. Levels of anti-inflammatory cytokine TGF-β were higher in CD-1. The enzymes MAO-A, MAO-B and iNOS were upregulated in both strains upon MPTP-challenge. Enhancement in fracktalkine and hemeoxygenase-1, post-MPTP, may be neuronal compensatory signals. Most importantly, ultrastructural observations of elongated glial mitochondria vis-à-vis the shrunken ones in neurons, suggest upscaling of glial functions with neurotoxic consequences. Thus, glia could be key modulators of ageing and disease-susceptibility.
Competing Interest Statement
The authors have declared no competing interest.