Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression.
Treating adult male rats with subcutaneous pellets of dehydroepiandrosterone (DHEA) increased the number of newly formed cells in the dentate gyrus of the hippocampus, and also antagonized the suppressive of corticosterone (40 mg/kg body weight daily for 5 days). Neither pregnenolone (40 mg/kg/day), a precursor of DHEA, nor androstenediol (40 mg/kg/day), a major metabolite, replicated the effect of DHEA (40 mg/kg/day). Corticosterone reduced the number of cells labelled with a marker for neurons (NeuN) following a 28-day survival period, and this was also prevented by DHEA. DHEA by itself increased the number of newly formed neurons, but only if treatment was continued throughout the period of survival. Subcutaneous DHEA pellets stimulated neurogenesis in a small number of older rats ( approximately 12 months old). These results show that DHEA, a steroid prominent in the blood and cerebral environment of humans, but which decreases markedly with age and during major depressive disorder, regulates neurogenesis in the hippocampus and modulates the inhibitory effect of increased corticoids on both the formation of new neurons and their survival.
Department of Anatomy, University of Cambridge, Cambridge, CB2 3DY, UK.
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Karishma
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Herbert
D000367:Age Factors; D015114:Androstenediol / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018696:Neuroprotective Agents; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D015114:Androstenediol; D003345:Corticosterone