Objective: To establish the neural basis of varying susceptibility to MPTP in MPTP resistant CD-1 mice, susceptible C57BL/6 mice and their crossbreds; simulating the variable incidence of Parkinson’s disease (PD) in different ethnic populations.

Background: Asian-Indians are less vulnerable to PD than the Caucasians. Interestingly their admixed population is at much lesser risk. Here we study the molecular aspects governing this difference in populations using mice strains with differential resistance to MPTP induced toxicity.

Methods: The primary nigral dopaminergic characteristics and phenotypes such as neuronal numbers, neuronal size and tyrosine hydroxylase (TH) expression were studied using stereology, morphometry and densitometry, respectively, on TH immunostained midbrain sections and Western blotting in adult C57BL/6, CD-1 and their F1 crossbreds (n=6/group). Comparisons were made following four injections of 15 mg/kg MPTP-HCl in 10 ml/kg body wt. of saline, at 2hrs interval.

Results: The number of DA neurons in CD-1 and both the crosses were significantly higher compared to C57BL/6. DA neuronal morphology in crossbreds was comparable to CD-1, whereas the neurons of C57BL/6 were larger. TH expression in the crossbreds was significantly higher when compared to the parent strains; also confirmed by Western blots. MPTP administration resulted in approximately 60% loss of C57BL/6 DA neurons and only 15% loss in CD-1 mice. Interestingly, crossbreds did not show any loss of DA neurons. A significant neuronal shrinkage was noted only in C57BL/6, but not in CD-1 and the crossbreds. The surviving neurons show stable TH expression upon MPTP administration.

Conclusions: Our findings of higher basal numbers of dopaminergic neurons and relatively attenuated death of DA neurons in neurotoxic conditions in CD-1 mice provide anatomical evidence for its resistance to MPTP. The crossbreds are even better protected against MPTP, which is reflected as supernumerary nigral neurons, absence of neuronal death and unaltered morphology following MPTP injection. A similarity in anatomical substrates and molecular mechanisms of neuroprotection may be envisaged in the Anglo-Indians. This animal model of admixture provides an interesting experimental paradigm to study the molecular mechanisms pertinent to the human phenomenon of differential prevalence of Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/f1-crossbreds-of-c57bl6-and-cd-1-mice-demonstrate-resistance-to-1-methyl-4-phenyl-1236-tetrahydropyridine-mptp-induced-nigral-neurodegeneration/