Regenerative potential of allopregnanolone

Jun Ming Wang, Lifei Liu, Ronald W. Irwin, Shuhua Chen, Roberta Diaz Brinton

Research output: Contribution to journalReview articlepeer-review

83 Scopus citations

Abstract

The neuroendocrine status of the brain has been linked to the quality of the aging process, to the risk of Alzheimer's disease and to progression of neurodegenerative pathology. Data from multiple levels of analysis ranging from in vitro cellular models to in vivo animal models to clinical investigations indicate that the decline of neurosteroids play a key role in successful aging and prevention of neurodegenerative disease Alzheimer's. Among the neurosteroids in decline during aging is allopregnanolone (APα, a metabolite of progesterone, which is reduced in the serum, plasma and brain of aged vs. young subjects. Further, Alzheimer's disease (AD) victims exhibit an even greater reduction in plasma and brain levels of APα relative to age-matched neurologically normal controls. Our earlier work has shown that APα is a neurogenic agent for rodent hippocampal neural progenitors and for human neural progenitor cells derived from the cerebral cortex. Our ongoing research seeks to determine the neurogenic potential of APα in the triple transgenic mouse model of Alzheimer's disease (3×TgAD) as AD related pathology progresses from imperceptible to mild to severe. Initial analyses suggest that APα may maintain the regenerative ability of the brain, modify progression of AD related pathology and reverse learning and memory deficits in 3×TgAD mice. This review summarizes current APα research in different animal models, neural progenitor regeneration within a degenerative milieu and the challenge for developing neuroregenerative therapeutics.

Original languageEnglish (US)
Pages (from-to)398-409
Number of pages12
JournalBrain Research Reviews
Volume57
Issue number2
DOIs
StatePublished - Mar 14 2008
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Neurodegenerative disease
  • Neurogenesis
  • Neuroregenerative therapeutics
  • Neurosteroids
  • Triple transgenic AD mouse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Regenerative potential of allopregnanolone'. Together they form a unique fingerprint.

Cite this