Age-related dopaminergic integrity in the SNpc and VTA: morphometric and volumetric findings in marmoset (Callithrix jacchus)

Abstract

Given a convergence of evidence indicating age-related vulnerability in nuclei associated with basal ganglia circuits, understanding the pattern of normal aging in non-human primates is essential for basic and applied research. To address this, we examined the age-dependent vulnerability of dopaminergic cells in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) of marmoset through morphoquantitative analysis of cytoarchitecture. Thus, we selected brain tissue from adult and aged marmosets processed for tyrosine hydroxylase (TH) immunohistochemistry. We estimated regional volume and counted TH-immunopositive (TH⁺) neurons in the SNpc and VTA. Statistical comparisons used permutation tests and Spearman's tests to analyze differences between age groups. Although Spearman's correlation test showed a negative correlation between regional volume and age and between TH⁺ cell number and age, no significant differences were found in either the permutation test or Spearman's correlation for TH + neuronal number and for regional volume between the age groups for both nuclei. We concluded that aging in marmosets does not lead to significant loss of dopaminergic neurons or measurable volumetric reduction in the SNpc or VTA. Our results highlight the importance of understanding physiological aging in contrast to models characterized by structural degeneration, such as those found in pathological conditions. Understanding, in a promising experimental model as marmoset, the pattern of vulnerability and resilience of dopaminergic regions fills gaps in the literature and opens avenues for understanding molecular and functional changes related to aging.