Objective: To delineate the contribution of neuronal-dendritic structure in the substantia nigra and striatum, in conferring differential susceptibility to Parkinson’s disease, using two genetically distinct mice strains.

Background: Loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) that results in reduction in striatal DA leads to Parkinson’s disease (PD). Epidemiological studies report that PD prevalence is higher among Caucasians than Asian-Indians. Due to lack of availability of human tissues for comparisons, we conducted detailed investigations on mice using MPTP. Our studies report that very similar to the humans; the C57BL/6J mice with lesser number of neurons and astroglia were more susceptible to MPTP, while the CD-1 mice with more DA neurons and reduced DA neuron death, were resistant. Neuronal morphology is another important parameter in pathogenesis. Structural alterations lead to differences in their functional attributes, as size and surface area determine their recruitment priority for executing different motor and cognitive tasks that are impaired in PD. Golgi staining is the best available technique to study alterations in dendritic arborisation, as histomorphological evidence.

Method: The mice striatal and nigral segments of C57BL/6J and CD-1 mice (n=12) were subjected to Golgi-Cox staining protocol followed by Neurolucida based tracing as well as Sholl’s analysis. We focussed on the alterations in dendritic processes of striatal medium spiny neurons (MSNs) and DA neurons following MPTP challenge.

Results: The dendritic processes of striatal MSNs and DA neurons were smaller in the control CD-1 than C57BL/6J, which further reduced after MPTP treatment in both regions. The branching, as seen by the number of intersections and nodes, was also lesser in CD-1 than C57BL/6J; which decreased in response to MPTP in both the regions. Unlike CD-1, C57BL/6J showed no alterations following MPTP.

Conclusion: Our results raise the likelihood that the surviving neurons of C57BL/6J continue to have larger arborisation and hence cell death may persist, which is known to stabilize by 7 days post-MPTP. The CD-1 neurons shrink in size. In view of reduced DA neuron death in CD-1, this is likely to be a degenerative signature or a survival mechanism. Similar structural dynamism may likely exist in the resistant human ethnic populations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-neuronal-morphology-to-determine-the-differential-susceptibility-to-parkinsons-disease-using-mptp-in-two-genetically-distinct-mice-strains/