UBC Faculty Research and Publications

Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner Duarte-Guterman, Paula; Lieblich, Stephanie E.; Wainwright, Steven R.; Chow, Carmen; Chaiton, Jessica A.; Watson, Neil V. (Neil Verne), 1962-; Galea, Liisa A. M.


Androgens (testosterone and dihydrotestosterone) 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 females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone (DHT), a potent androgen, on neurogenesis in young adult and middle-aged males and females. 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 days. We evaluated cell proliferation (Ki67) and survival of new neurons (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased the number of BrdU+ cells in young males but surprisingly not in middle-aged male rats or in young and middle-aged females. In middle age, DHT increased the proportion of BrdU/NeuN cells, an effect driven by females. AR 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.

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