Neural androgen receptors affect the number of surviving new neurons in the adult dentate gyrus of male mice

Abstract

Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurons within the hippocampus is modulated by androgen action via the androgen receptor (AR), however it is not known whether this holds true in mice. Furthermore, evidence is mixed as to whether androgens act in neural tissue or via peripheral non-neural targets to promote hippocampal neuron survival. We evaluated whether androgen action via AR underlies the survival of new neurons in mice, and asked whether increasing AR selectively in neural tissue would increase new neuron survival in the hippocampus. We used the cre-loxP system to overexpress AR only in neural tissues (Nestin-AR), and these males were compared to wildtype males, and control males with one of the two mutations required for overexpression. Mice were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, the proliferation (Ki67) and survival (BrdU) of new neurons were evaluated in the dorsal and ventral dentate gyrus. DHT treatment increased the survival of new neurons in the entire hippocampus in wildtype mice and control mice that only have one of two necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurons in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wildtype or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neuron survival is nonlinear.

This article is protected by copyright. All rights reserved.

http://ift.tt/2sf9T4m