Impact of very old age on hypothalamic dopaminergic neurons in the female rat:: A morphometric study

Dopaminergic neurons of the A(12) (tuberoinfundibular dopaminergic system) and A,, (periventricular dopaminergic system) hypothalamic areas exert a tonic inhibitory control of prolactin secretion. Tuberoinfundibular dopaminergic system neuron function is known to decline during aging in rats, but little is known about the impact of extreme age on neuron number and morphology in the two systems. We morphometrically assessed the neurons of the tuberoinfundibular dopaminergic system and the periventricular dopaminergic system in female rats 6 (young, Y), 24 (old, 0), and 30-32 (senescent, S) months old. Serial coronal sections of fixed hypothalami were immunohistochemically labeled for tyrosine hydroxylase, and immunoreactive perikarya from the A(12) and A(14) areas were quantitatively characterized and compared among the three age groups. Radioimmunoassay was used to measure serum prolactin. The number of A(12) tyrosine hydroxylase-immunoreactive perikarya showed a steady decline with age, whereas the number of A(14) tyrosine hydroxylase-immunoreactive perikarya remained stable from young to old age but showed a sharp drop in the senescent rats. In the old rats, tyrosine hydroxylase-immunoreactive neuronal area (A(12) = 135.37 and A(14) = 158.79 mum(2)) was significantly higher than that of young (A(12) = 72.56 and A(14) = 99.7 mum(2)) and senescent animals (A(12) = 95.5 and A(14) = 106.5 mum(2)). Densitometric assessment of median eminence tyrosine hydroxylase immunoreactivity revealed a steady age-related reduction of tyrosine hydroxylase content in the median eminence. Serum prolactin levels increased steadily with age. We conclude that, in the female rat, aging brings about a progressive loss of both tuberoinfundibular dopaminergic system and periventricular dopaminergic system neurons, which becomes more conspicuous at extreme ages. (C) 2003 Wiley-Liss, Inc.