Baseline striatal and nigral interneuronal protein levels in two distinct mice strains differ in accordance with their MPTP susceptibility.

ABSTRACT

Epidemiological studies reveal an ethnicity-based bias in prevalence of Parkinson's disease (PD), deriving from the differences that exist between Caucasians and African or Asian populations. Experimental mice models provide a scope to analyse the cellular mechanisms of differential susceptibility to PD. C57BL/6J mice, for instance, are more susceptible to MPTP-induced Parkinsonism whereas CD-1 mice are resistant. In PD-pathogenesis, interneuronal contribution is also likely, although they comprise only 5-10% of the striatal cells. The interneurons harbour calcium binding proteins, like calretinin (Cal-R) and parvalbumin (PV), which are crucial in Ca2+ homeostasis for preventing calcium-induced excitotoxicity. GAD-67-immunoreactive interneurons are the other prominent set of GABAergic interneurons. In PD, dopamine loss up-regulates GAD-67 expression in striatal projection neurons and other basal ganglia circuit. We studied the possible contribution of interneurons in determining variable susceptibility by assessing the expression of calretinin, PV and GAD-67 in both striatum and substantia nigra pars compacta (SNpc) in two distinct mice strains, i.e. C57BL/6J and CD-1 under normal conditions, using unbiased stereology for quantification of immunoreactive cells and immunoblotting. The vulnerable C57BL/6J had lesser basal parvalbumin expression in both nigra and striatum whereas the calretinin levels were low only in the striatum. GAD-67 expression showed no perceptible differences in the striatum or SNpc of either of the strains. Differential expression of calcium buffering/binding proteins under normal physiological condition proffers a role for interneurons in the differential susceptibility to PD. Thus, even the baseline susceptibility indices i.e. without using the neurotoxin; can provide vital mechanistic insights into PD pathogenesis.