The nigrostriatal system and aging

Age-correlated changes in neurotransmitter systems of the basal ganglia have been postulated to contribute to the disruption of motor function and balance associated with aging. This report compared the morphology of nigrostriatal dopamine (DA) neurons of the substantia nigra and ventral tegmental area of the C57B1/6N Nia mouse with the morphology of DA neurons of the nigrostriatal pathway in aged human brain and in one case diagnosed to have senile dementia of the Alzheimer's type (SDAT). Age-correlated changes in fibers of the nigrostriatal pathway in the aged mouse are characterized by an increase in the number of large, fluorescent axonal dilations. Similar axonal swellings were seen in aged human brain. In addition, postmortem SDAT brain was characterized by the presence of large patches or tangles of DA-containing fibers. In the C57B1/6N Nia mouse, age-correlated morphological changes were characterized by a progressive accumulation of cytoplasmic lipofuscin granules and a markedly reduced DA content per cell is determined visually by histofluorescence. Most neurons of the pars compacta of the substantia nigra in postmortem human brain were nonfluorescence and contained heavy deposits of neuromelanin in their cytoplasm. These data suggest that age-correlated morphological changes in fibers of the nigro-striatal system of the aged C57B1/6N Nia mouse are similar in appearance to fibers in the aged human brain and that morphological related changes in dopaminergic cells may play a role in the disruption of motor function associated with advancing age. In addition, the presence of large tangles or patches of DA fibers in postmortem SDAT brain suggests that subcortical DA-containing neurons may also be affected in SDAT.