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

Donatella Caruso, Anna M. Barron, Meghan A. Brown, Federico Abbiati, Paloma Carrero, Christian J. Pike, Luis M. Garcia-Segura, Roberto C. Melcangi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1080-1089
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

ASJC Scopus Subject Areas

  • General Neuroscience
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Keywords

  • Alzheimer's disease
  • GABA-A receptors
  • Limbic region
  • Metabolic pathways
  • Progesterone
  • Testosterone

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