Objective: To evaluate the changes in the neuronal arborization of the medium spiny neurons of striatum & substantia nigra neurons,  in response to MPTP in C57Bl/6J and CD-1 mice and their crossbred

Background: Epidemiological studies report higher PD prevalence among Caucasians than Asian-Indians; and five-times lower prevalence in Anglo Indians (1). While reminiscing this phenomenon in mice we reported that C57BL/6J strain with fewer nigral neurons was more susceptible to MPTP and showed Parkinsonian symptoms, while CD-1 and their admixed F1-progeny (F1X1, F1X2) with more nigral neurons and lesser neuron death (2), were resistant. Structural alterations affect functional attributes, as size determines their recruitment priority for executing motor and cognitive tasks, impaired in PD. Golgi staining (3) is the best available technique to study alterations in dendritic arborisation, as histo-morphological evidence. Synaptic and other transporter and transport proteins may play a major role in fabricating the neuronal architecture

Method: The striatal and nigral regions of C57BL/6J, CD-1 and F1X2 mice (n=5 mice) with or without MPTP administration were subjected to Golgi-Cox staining, followed by Neurolucida based tracing, Sholl’s analysis and Image-J based Spine count

Results: The dendritic processes were shorter and the complexity of striatal MSNs and DA neurons were reduced in response to MPTP, in C57BL/6J. However, in CD-1 the reduction was limited to MSNs. Interestingly, in F1X2, a small increase in dendritic length was observed. The branching pattern, as seen by the number of intersections, remained stable in both regions in C57BL/6J. Similar to the alterations in the dendritic length, CD-1 mice showed significant increase in the number of spines largely mushroom types following MPTP

Conclusion: The reduction in dendritic arborisation and branching pattern in both regions in C57BL/6J may be a degenerative signature. The MPTP-induced alterations in dendritic length, complexity and spine counts in CD-1 & F1X2 MSNs may cogitate structural reorganization and neural plasticity respectively, at the level of striatum, which could be either a neurodegenerative signal or a neuroprotective strategy. Thus, structural reorganization is an important parameter in resistance to PD pathology. It might be useful to lay eyes on expression of synaptic proteins and ultrastructural features

References: 1 Ragothaman, M., Murgod, U.A., Gururaj, G., Kumaraswamy, S.D. and Muthane, U., 2003. Lower risk of Parkinson’s disease in an admixed population of European and Indian origins. Movement disorders: official journal of the Movement Disorder Society, 18(8), pp.912-914.
2 Vidyadhara, D.J., Yarreiphang, H., Abhilash, P.L., Raju, T.R. and Alladi, P.A., 2016. Differential expression of calbindin in nigral dopaminergic neurons in two mice strains with differential susceptibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Journal of chemical neuroanatomy, 76, pp.82-89.
3 Zhang, H., Weng, S.J. and Hutsler, J.J., 2003. Does microwaving enhance the Golgi methods? A quantitative analysis of disparate staining patterns in the cerebral cortex. Journal of neuroscience methods, 124(2), pp.145-155.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mptp-induced-structural-reorganization-of-neurons-in-mice-basal-ganglia-verifying-the-sequelae-of-differential-toxicity/