Journal
NEUROBIOLOGY OF AGING
Volume 34, Issue 4, Pages 1080-1089Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.10.007
Keywords
Progesterone; Testosterone; Metabolic pathways; Alzheimer's disease; Limbic region; GABA-A receptors
Categories
Funding
- Fondazione San Paolo [PF-2009.1180]
- NIH [AG05142]
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Although neuroactive steroids exert neuroprotective actions in different experimental models of neurodegenerative diseases, including those of Alzheimer's disease (AD), their relationships with aged related physiologic and pathologic brain changes remain to be clarified. In this study the levels of pregnenolone, dehydroepiandrosterone, progesterone, dihydroprogesterone, tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, 17 alpha-estradiol, and 17 beta-estradiol were assessed in the limbic region of young adult (7 months) and aged (24 months) male wild type and triple transgenic AD mice. Age related neuropathological changes in AD brains, such as beta-amyloid accumulation and gliosis, were associated with modified levels of specific neuroactive steroids and particularly with changes in the levels of progesterone and testosterone metabolites. The altered levels of neuroactive steroids in aged AD brains might impact on the activation of neuroprotective signaling mediated by classic and nonclassic steroid receptors, like the gamma-aminobuttyric acid (GABA)-A receptor. (C) 2013 Elsevier Inc. All rights reserved.
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