Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner

Abstract

Androgens (testosterone and DHT) increase adult hippocampal neurogenesis by increasing survival of new neurons in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in female rats and whether the effect is age-dependent. We investigated the effects of DHT, a potent androgen, on neurogenesis in young adult and middle-aged male and female rats. Rats were gonadectomized and injected with the DNA synthesis marker bromodeoxyuridine (BrdU). The following day, rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and survival of new neurons (BrdU and BrdU/NeuN) in the hippocampus of male and female rats by using immunohistochemistry. As expected, DHT increased the number of BrdU+ cells in young males but surprisingly not in middle-aged males or in young and middle-aged females. In middle age, DHT increased the proportion of BrdU/NeuN cells, an effect driven by females. Androgen receptor expression also increased with aging in both female and male rats, which may contribute to a lack of DHT neurogenic effect in middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.