Objective: To delineate the age-associated changes in microglial morphotypes in the substantia nigra pars compacta (SNpc) of C57BL/6J and CD-1 mice and alterations in response to MPTP

Background: Microglia are key players in the pathogenesis of Parkinson’s disease (PD), for which, age is a major risk factor. As neurons age, glia undergo changes in phenotype and functions, resulting in neuroinflammation. We recapitulated the phenomenon of differential susceptibility to PD by comparing the degenerative events in the SNpc of MPTP-resistant CD-1 and MPTP- susceptible C57BL/6J mice. Here we performed detailed examinations of changes in microglial phenotypes, with age and in response to the neurotoxin MPTP

Method: We studied both the strains (n=3-5/strain/experimental condition) at 3 age-periods i.e. 15-17w (young),12 months (middle-aged) and 18 months (old). They received either normal saline or 4 doses of MPTP-HCl (15mg/kg, i.p.) at 2-h intervals. 7 days post-MPTP, mice brains were harvested and 40µ thick midbrain cryosections were sequentially immunostained for TH and Iba-1. Morphotyping was performed on captured images by LAS-X software and “Windows-based” image analysis. Mixed effects model with Tukey’s post-hoc analysis was applied for statistics

Results: The C57BL6J and CD-1 did not show any significant differences in the no. of microglia/field at baseline, at young and middle age; whereas at old age the CD-1 had more microglia.Type-1 microglia were significantly more in MPTP-injected C57BL/6J at young (C57BL/6J vs CD-1;**p<0.01) and middle age (C57BL/6J vs CD-1;*p<0.05), but the differences thinned at old age. The type-4 were significantly more in MPTP-injected old CD-1 mice (MPTP;CD-1 vs C57BL/6J **p<0.01). Type 2 and 3 microglia remained comparable. The C57BL/6J-MPTP showed a significant increase (MPTP;C57BL/6J vs CD-1;***p<0.0008) at middle age

Conclusion: The increase in type-1 microglia in MPTP-treated C57BL/6J at young and middle age suggests recruitment and/or migration of microglia and thus activation of neuroinflammatory cascades. The frank microgliosis in C57BL/6J at middle age hints at higher susceptibility to MPTP, while reduced microgliosis at old age may reflect subthreshold or failed response. The differences in microglial phenotypes with age and in response to MPTP may likely aid the understanding of differential susceptibility to PD

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-associated-changes-in-microglial-morphology-and-its-role-in-deciphering-susceptibility-to-parkinsons-disease/