Differential effects of advancing age on neurotransmitter cell loss in the substantia nigra and striatum of C57BL/6N mice.

The present study was carried out to examine the extrapyramidal motor system of C57BL/6N mice for age-related cell loss in cholinergic neurons of the striatum (ST) and dopaminergic (DA) neurons of the substantia nigra (SN). Immunocytochemistry using antibodies against tyrosine hydroxylase (TH) or choline acetyltransferase (CAT) were used to identify DA or cholinergic neurons of the SN and ST in 6 age groups of young (3 months), middle (6, 10, 20 months) and old (25, 30 months) aged mice. We found that while there was a small decline (11%) in the total number of DA neurons of the SN with age, this decrease did not reach statistical significance. In contrast, the total number of cholinergic neurons of the ST significantly decreased between 25 and 30 months of age with the largest cell loss (38%) found in the rostral ST. In addition, the loss of cholinergic neurons in 30-month-old mice was paralleled by a decline in the mean cross-sectional area of the cell soma and nucleus of remaining cholinergic neurons. These data suggest that advancing age has a differential effect on neurotransmitter neurons of the SN and ST and supports the notion that cell loss is not an inevitable characteristic of senescence but is brain region- and cell type-specific. In addition, these data are consistent with the hypothesis that the proliferation of striatal dendrites described previously in aged C57BL/6N mice may result, in part, from a compensatory growth of these processes secondary to age-related cell loss of striatal neurons.