Objective: To examine the age-related changes in tyrosine hydroxylase (TH), vesicular monoamine transporter2 (VMAT2), post-synaptic density protein-95 (PSD-95) and dopamine receptors (D1R, D2R) expression in the human striatum.

Background: Age is a major risk factor for Parkinson’s disease (PD). The disease prevalence also varies by ethnicity, where Asian-Indians and non-whites are less susceptible than Caucasians. Earlier reports have shown nigral preservation in aging Asian-Indians. While few studies on histopathological changes in the striatum are reported in the Caucasians, the alterations in Asian-Indians are not well defined.

Method: Archival striatal tissues were procured from normal aging subjects succumbing to road traffic accidents. Formalin-fixed paraffin embedded 5μm sections were immunohistochemically stained for PSD-95, D1R and D2R and analysed by densitometry (ImageJ, NIH, USA). Besides, 40μm cryosections were immunofluorescently labelled for TH and VMAT2 and the expression was measured in terms of fluorescence intensity, using LASX software.

Results: TH and VMAT2 stained more intensely in the matrix, compared to striosome. Pearson’s correlation coefficient assisted statistics suggested a slight age-related increase in TH [r(24)= .168,p=.432], alongside a small reduction in VMAT2 expression  [r(21)= -.350,p=.119]. The area occupied by VMAT2 increased slightly [r(21)=.162, p=0.481]. A slight reduction in D1R [r(27)=-.093, p=.643] and increase in D2R [r(25)=.330,p=.106] was noted. With age, PSD-95 expression decreased significantly [r(29)= -.527,p=.003**].

Conclusion: The higher expressions of TH and VMAT2 in the matrix confirms the compartmental arrangement of the dopaminergic terminals. The slight alterations in DRs and TH, shows that the direct and indirect pathways of the striatum and the dopaminergic innervations are fairly preserved. The decrease in VMAT2, suggests the occurrence of subtle age-related neurodegenerative changes. The small increase in the VMAT2-occupied area might be a compensatory action. The significant reduction in PSD-95, shows the vulnerability of the post synaptic densities towards degenerative sequelae. These observations emphasize the subliminal striatal pathology in our aging populace and explain the mechanisms behind the lower prevalence of PD in Asian-Indians.

Data partially presented at AOCN NPSICON, 24-26^th Sept & IAN, 16-19^th Dec.’21.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-associated-changes-in-the-striatal-proteins-in-aging-asian-indians/