Objective: To evaluate the electrophysiological and motor behavioural correlates of strain-dependent differential susceptibility of mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the role of admixing thereon.

Background: Asian-Indians are less vulnerable to Parkinson’s disease (PD) than the Caucasians. Interestingly their admixed population, the Anglo-Indians are at much lesser risk. We studied this phenomenon using MPTP-susceptible C57BL/6J mice, MPTP-resistant CD-1 and their crossbreds. The latter groups show differences in nigrostriatal cytomolecular features that may assign resistance to MPTP; which is likely in humans too.

Methods: Local field potentials (LFPs) from dorsal striatum were recorded from C57BL/6J, CD-1 and their F1 crossbred mice using deep steel electrodes. Saline controls and MPTP groups (15 mg/kg MPTP-HCl, intraperitoneal, 4 injections, 2h interval) were compared pre and post injection. Expression of nigral dopaminergic (DA) calbindin D-28K, a modulator of striatal activity through nigral projections was evaluated using immunohistochemistry. Motor co-ordination was assessed using rotarod and grip strength parameters.

Results: Basal striatal LFPs were significantly higher in crossbreds than the parent strains. MPTP injection enhanced the activity in delta (0.5-4 Hz) and low beta (12-16 Hz) ranges in C57BL/6J. It caused a significant increase in CD-1 across all frequency bands up to high beta (0.5-30 Hz). Interestingly, in the crossbreds it remained unaltered in response to MPTP. Basal calbindin expression in nigral DA neurons of C57BL/6J was low, which depleted further upon MPTP injection, but the crossbreds showed upregulation of the already higher levels. MPTP impaired the rotarod performance and grip strength of only the C57BL/6J.

Conclusions: We provide the first evidence for increased striatal β-oscillations in MPTP mice model (C57BL/6J), as seen in PD patients. Higher power in CD-1 might be compensatory; as noted by others in monkeys during pre-symptomatic PD. Augmented basal striatal firing and maintenance in toxic conditions in crossbreds, both agree with our earlier cytomolecular observations of superior neuroprotection. Upregulated nigral calbindin might help maintain striatal activity through sustained dopamine release, by buffering MPTP mediated calcium overload in nigra. Thus, preserved motor behaviour despite MPTP-toxicity in CD-1 and the crossbreds may result from compensated striatal LFPs. We envisage similar mechanisms in human phenomenon of differential PD prevalence and its modulation in the admixed, as seen in the Anglo-Indians.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/no-mptp-induced-behavioral-deficits-or-striatal-field-potential-alterations-in-crossbreds-of-mptp-susceptible-and-mptp-resistant-mice-strains/