Dopaminergic neurons in the mediobasal hypothalamus of old rats: Evidence for decreased affinity of tyrosine hydroxylase for substrate and cofactor

The effect of aging on the activity of tyrosine hydroxylase (TH) and on the number of TH-positive perikarya in the hypothalamus was studied in old and young female rats. The activity of TH in the mediobasal hypothalamus (MBH) of old rats was significantly (P < 0.025) less than that in young rats. In old rats, the K_m of TH for tyrosine as well as cofactor, 6-methyl-5,6,7,8-tetrahydropterine (6MPH₄), was markedly greater than the K_m in young rats. The maximal velocity was only slightly reduced in old animals. Contiguous coronal sections of the brain of an old and a young female rat were immunocytochemically stained for TH, and the TH-positive perikarya in the hypothalamus were counted. In the circumventricular region, 6793 TH-positive perikarya were present in the young brain and 6632 in the old brain. In the arcuate region, 2868 and 2760 TH-positive perikarya were counted in the young and old brain, respectively. It is concluded that the reduced TH activity in the MBH of old rats is not a consequence of a reduction in the number of TH-positive perikarya in the arcuate or circumventricular regions of the hypothalamus but is due to a reduction in the affinity of TH for its substrate and cofactor.