Aging mildly affects dendritic arborisation and synaptic protein expression in human substantia nigra pars compacta

Abstract

The protein α-synuclein, a major component of Lewy bodies in nigral neurons of aged and Parkinson's disease (PD) patients, normally co-localizes with synaptophysin and regulates the pool of synaptic vesicles. Our earlier study on substantia nigra pars compacta (SNpc) in an Asian-Indian population, demonstrated an age-associated linear but non-logarithmic increase in soluble α-synuclein without any loss of nigral neurons. Another distinctive finding was the presence of activated microglia in the ventrolateral region of the aged nigra, suggesting sub-threshold neurodegeneration. Since microglia prune dendrites, we evaluated the alterations in dendritic arborisation in the SNpc from autopsied midbrains of Asian-Indians through aging, using Golgi-Kopsch protocol. Further, we evaluated the expression of synaptic proteins, synaptophysin and synaptotagmin-11 as parallel markers of synaptic transmission anomalies. The dendritic arborization pattern was typical of large multipolar neurons. A subtle but non-significant decline in parameters like dendritic length and number of intersections was noted. Thus, the alterations were milder than those reported in PD. In the neurons of the young (till 10 years), faint cytoplasmic immunoreactivity of synaptic proteins was noted. In the adults and elderly, it was membrane-bound or appeared as punctae within neuropil. Both proteins showed a slight age-related decline, suggesting a mild decrease in the synaptic vesicular traffic, affecting the dopamine transmission with age that may manifest as minor motor disabilities in the elderly. Mapping the differences in synaptic profiles in differentially susceptible ethnic populations, could reveal interesting insights. Thus, nigra of aged individuals and PD patients share pathogenic features that differ in magnitude.