Role of the Gonads in the Histologic Aging of the Hypothalamic Arcuate Nucleus

The effect of aging on microglial and astrocytic activity in the hypothalamic arcuate nucleus was measured in young and middle-aged Wistar rats and C57BL/6J mice. These putative correlates of neuronal degeneration increased significantly between 6 and 14 months of age in intact female and male rats, and between 4 and 13 months in female mice. Although astrocytic activity increased steadily between 4, 8.5, and 14 months in female rats, microglial activity did not increase until 14 months. Because glial hyperactivity can be produced in young rats by exogenous estrogen, long-term gonadectomized animals were examined to determine if its development during normal aging is also dependent on exposure to gonadal steroids. Gonadectomy at 2 months of age significantly suppressed gliosis in older female rats and mice, but produced only a slight (nonsignificant) decrease in male rats. These data indicate that gliosis occurs spontaneously in the aging arcuate nucleus. Its development in the female is primarily dependent on chronic exposure to an ovarian product, presumably estradiol. However, in the male the testes play little if any role. The differential rates of astrocytic and microglial activity in female rats may reflect differential sensitivity to the ovarian product(s) responsible for their development.