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Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease


Year of Publication:
Contact PI Name:
Roberta Diaz Brinton
Contact PI Affiliation:
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, and Program in Neuroscience, University of California, Los Angeles, California, USA
Jun Ming Wang, Chanpreet Singh, Lifei Liu, Ronald W. Irwin, Shuhua Chen, Eun Ji Chung, Richard F. Thompson
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Kenneth T. and Eileen L. Norris Foundation
Alzheimer's Drug Discovery Foundation (ADDF)
Study Goal and Principal Findings:

 The goal of this study was to obtain preclinical proof-of-concept that allopregnanolone (APα) can function as a regenerative factor with an impact on cognitive function in AD. To  this end the authors investigated the efficacy of APα  in promoting neurogenesis in the hippocampal subgranular zone (SGZ), and reversing learning and memory deficits in the 3xTg AD mouse model. Using this AD model, the authors characterized APα concentration in brain and serum, basal level of neurogenesis, and  impact on cognitive function mice at 3 months of age. Data showed that APα, after a single injection, reversed deficits in SGZ neurogenesis, reversed cognitive deficits and restored learning and memory performance to the level of normal non-Tg mice. In addition, APα-induced survival of neural progenitors was significantly correlated with APα-induced memory performance.  At 3 months, basal level of neuroprogenitors  in the SGZ of 3xTgAD mice was significantly lower relative to non-Tg mice, despite the lack of evident AD pathology.These findings suggest that early neurogenic deficits, which were evident before immunodetectable Aβ, may contribute to the cognitive phenotype of AD and that APα could serve as a regenerative therapeutic to prevent or delay neurogenic and cognitive deficits associated with mild cognitive impairment and Alzheimer’s disease.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Hormone
Therapeutic Agent:
Allopregnanolone (APα)
Therapeutic Target:
GABA-A Receptor

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
129/Sv × C57BL/6
Model Type:
Strain/Genetic Background:
129/Sv × C57BL/6

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Trace Eye Blink Conditioning
Neural Progenitor Cell Proliferation Markers
Brain-beta Amyloid Peptides
Drug Concentration-Plasma
Drug Concentration-Brain