dc.contributor.author | Ding, Fan | |
dc.contributor.author | Yao, Jia | |
dc.contributor.author | Zhao, Liqin | |
dc.contributor.author | Mao, Zisu | |
dc.contributor.author | Chen, Shuhua | |
dc.contributor.author | Brinton, Roberta Diaz | |
dc.date.accessioned | 2015-05-28T16:39:37Z | |
dc.date.available | 2015-05-28T16:39:37Z | |
dc.date.issued | 2013-03-26 | |
dc.identifier.citation | Ding, Fan, Jia Yao, Liqin Zhao, Zisu Mao, Shuhua Chen, and Roberta Diaz Brinton. "Ovariectomy Induces a Shift in Fuel Availability and Metabolism in the Hippocampus of the Female Transgenic Model of Familial Alzheimer's." PLoS ONE 8.3 (2013): n. pag. http://dx.doi.org/10.1371/journal.pone.0059825. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17874 | |
dc.description | This is the published version. Copyright 2013 Public Library of Science. | en_US |
dc.description.abstract | Previously, we demonstrated that reproductive senescence in female triple transgenic Alzheimer's (3×TgAD) mice was paralleled by a shift towards a ketogenic profile with a concomitant decline in mitochondrial activity in brain, suggesting a potential association between ovarian hormone loss and alteration in the bioenergetic profile of the brain. In the present study, we investigated the impact of ovariectomy and 17β-estradiol replacement on brain energy substrate availability and metabolism in a mouse model of familial Alzheimer's (3×TgAD). Results of these analyses indicated that ovarian hormones deprivation by ovariectomy (OVX) induced a significant decrease in brain glucose uptake indicated by decline in 2-[18F]fluoro-2-deoxy-D-glucose uptake measured by microPET-imaging. Mechanistically, OVX induced a significant decline in blood-brain-barrier specific glucose transporter expression, hexokinase expression and activity. The decline in glucose availability was accompanied by a significant rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate generation and utilization. In parallel, a significant rise in ketone body concentration in serum occurred which was coupled to an increase in neuronal MCT2 expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was paralleled by a significant increase in Aβ oligomer levels. 17β-estradiol preserved brain glucose-driven metabolic capacity and partially prevented the OVX-induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose transporter expression and gene expression associated with aerobic glycolysis. 17β-estradiol also partially prevented the OVX-induced increase in Aβ oligomer levels. Collectively, these data indicate that ovarian hormone loss in a preclinical model of Alzheimer's was paralleled by a shift towards the metabolic pathway required for metabolism of alternative fuels in brain with a concomitant decline in brain glucose transport and metabolism. These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.subject | Glucose metabolism | en_US |
dc.subject | Glucose | en_US |
dc.subject | Ovariectomy | en_US |
dc.subject | Hexokinases | en_US |
dc.subject | Ketones | en_US |
dc.subject | bioenergetics | en_US |
dc.subject | Alzheomer disease | en_US |
dc.subject | Hormones | en_US |
dc.title | Ovariectomy Induces a Shift in Fuel Availability and Metabolism in the Hippocampus of the Female Transgenic Model of Familial Alzheimer's | en_US |
dc.type | Article | |
kusw.kuauthor | Zhao, Liqin | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1371/journal.pone.0059825 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |