Document Detail


Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid.
MedLine Citation:
PMID:  21514693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we demonstrated that reproductive senescence was associated with mitochondrial deficits comparable to those of female triple-transgenic Alzheimer's mice (3xTgAD). Herein, we investigated the impact of chronic ovarian hormone deprivation and 17β-estradiol (E2) replacement on mitochondrial function in nontransgenic (nonTg) and 3xTgAD female mouse brain. Depletion of ovarian hormones by ovariectomy (OVX) in nontransgenic mice significantly decreased brain bioenergetics, and induced mitochondrial dysfunction and oxidative stress. In 3xTgAD mice, OVX significantly exacerbated mitochondrial dysfunction and induced mitochondrial β-amyloid and β-amyloid (Aβ)-binding-alcohol-dehydrogenase (ABAD) expression. Treatment with E2 at OVX prevented OVX-induced mitochondrial deficits, sustained mitochondrial bioenergetic function, decreased oxidative stress, and prevented mitochondrial β-amyloid and ABAD accumulation. In vitro, E2 increased maximal mitochondrial respiration in neurons and basal and maximal respiration in glia. Collectively, these data demonstrate that ovarian hormone loss induced a mitochondrial phenotype comparable to a transgenic female model of Alzheimer's disease (AD), which was prevented by E2. These findings provide a plausible mechanism for increased risk of Alzheimer's disease in premenopausally oophorectomized women while also suggesting a therapeutic strategy for prevention.
Authors:
Jia Yao; Ronald Irwin; Shuhua Chen; Ryan Hamilton; Enrique Cadenas; Roberta Diaz Brinton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-04-22
Journal Detail:
Title:  Neurobiology of aging     Volume:  33     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-10-24     Revised Date:  2013-08-19    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1507-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA.
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxyacyl CoA Dehydrogenases / metabolism*
Aging / metabolism*
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism*
Animals
Brain / metabolism*
Estradiol / deficiency*
Female
Mice
Mice, Knockout
Mitochondria / metabolism*
Oxidative Stress
Grant Support
ID/Acronym/Agency:
2R01AG032236/AG/NIA NIH HHS; 5P01AG026572/AG/NIA NIH HHS; P01 AG026572-04/AG/NIA NIH HHS; R01 AG032236/AG/NIA NIH HHS; R01 AG032236-07/AG/NIA NIH HHS; R01 AG032236-08/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 50-28-2/Estradiol; EC 1.1.1.35/3-Hydroxyacyl CoA Dehydrogenases; EC 1.1.1.35/HSD17B10 protein, human
Comments/Corrections

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