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Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of Familial Alzheimer's

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2013
Contact PI Name:
Roberta Diaz Brinton
Contact PI Affiliation:
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Co-Authors:
Fan Ding, Jia Yao, Liqin Zhao, Zisu Mao, Shuhua Chen
Primary Reference (PubMED ID):
23555795
Funding Source:
National Institute on Aging (NIA)
Kenneth T. and Eileen L. Norris Foundation
Study Goal and Principal Findings:

In the present study, we investigated the impact of ovariectomy and 17b-estradiol replacement on brain energy substrate availability and metabolism in a triple transgenic mouse model of Alzheimer’s disease (3xTgAD). 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. 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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Hormone
Therapeutic Agent:
17beta-estradiol
PubMed
PubChem
DrugBank
ClinicalTrials
Patents
Therapeutic Target:
Estrogen Receptor
Open Targets
Pharos
Therapeutic Notes:
Estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism.

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1xTau
Model Name:
3xTg
ALZFORUM
Strain/Genetic Background:
C57BL6/129S

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
Biomarkers
Dose
Formulation
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
Experiment Notes

Inclusion/Exclusion Criteria: Only offspring from breeders that exhibit stable AD pathology were randomized into the study.

Outcomes

Outcome Measured
Outcome Parameters
Biochemical
3-oxoacid CoA Transferase (SCOT)
Amyloid Precursor Protein (APP)
Brain-beta Amyloid Oligomers
Glucose Transporter 1 (GLUT1)
Glucose Transporter 3 (GLUT3)
Glucose Uptake
Hexokinase II
Hexokinase II Activity
Lactate Dehydrogenase B (LDH B)
Lactate Dehydrogenase V (LDH V)
Monocarboxylate Transporter 2 (MCT 2)
Imaging
[18F]FDG-PET
Micro-Computed Tomography
Biomarker
Serum-beta Hydroxybutyrate
Toxicology
Body Weight
Tail Skin Temperature
Omics
Gene Expression Profile-Bioenergetics
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