title: Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats.
abstract: Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.
authors.forename: D K
authors.initials: DK
authors.lastname: Hamson
authors.forename: S R
authors.initials: SR
authors.lastname: Wainwright
authors.forename: J R
authors.initials: JR
authors.lastname: Taylor
authors.forename: B A
authors.initials: BA
authors.lastname: Jones
authors.forename: N V
authors.initials: NV
authors.lastname: Watson
authors.forename: L A M
authors.initials: LA
authors.lastname: Galea
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity; D013734:Androgen-Insensitivity Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000728:Androgens / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002369:Castration / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004351:Drug Resistance; D020249:Hormone Replacement Therapy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D043343:Testosterone Propionate / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D015415:Biomarkers; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D011944:Receptors, Androgen; D043343:Testosterone Propionate