| First Author | Yao J | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 8 | Pages | 1507-21 |
| PubMed ID | 21514693 | Mgi Jnum | J:188212 |
| Mgi Id | MGI:5439699 | Doi | 10.1016/j.neurobiolaging.2011.03.001 |
| Citation | Yao J, et al. (2012) Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid. Neurobiol Aging 33(8):1507-21 |
| abstractText | 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 17beta-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 beta-amyloid and beta-amyloid (Abeta)-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 beta-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. |
