Age-related changes in neuroactive steroid levels in 3xTg-AD mice

• Published in: Neurobiology of aging Vol. 34; no. 4; pp. 1080 - 1089
• Main Authors: Caruso, Donatella, Barron, Anna M, Brown, Meghan A, Abbiati, Federico, Carrero, Paloma, Pike, Christian J, Garcia-Segura, Luis M, Melcangi, Roberto C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2013
• Subjects: Age; Aging; Aging - metabolism; Alzheimer Disease - metabolism; Alzheimer's disease; Animal models; Animals; Brain; Dehydroepiandrosterone; Dihydrotestosterone; GABA-A receptors; Gliosis; Internal Medicine; Limbic region; Limbic System - metabolism; Metabolic pathways; Metabolites; Mice; Mice, Transgenic; Nervous system; Neurodegenerative diseases; Neurology; Neuroprotection; Neurosteroids; Pregnenolone; Progesterone; Receptors, Steroid - metabolism; Steroid hormone receptors; Steroids - metabolism; Testosterone; tetrahydroprogesterone; Tissue Distribution; Transgenic mice; Testosterone; Metabolic pathways; Progesterone; Alzheimer's disease; Limbic region; GABA-A receptors
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2012.10.007

Abstract 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, 5α-androstane-3α,17β-diol, 5α-androstane-3β,17β-diol, 17α-estradiol, and 17β-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 β-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.