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J Cereb Blood Flow Metab. 2014 Nov;34(11):1749-60. doi: 10.1038/jcbfm.2014.137. Epub 2014 Aug 6.

Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer's disease and the effect of lipoic acid: a 13C-NMR study.

Author information

1
Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
2
Enhanced Magnetic Resonance Laboratory, Huntington Medical Research Institutes, Pasadena, California, USA.
3
Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
4
Sanders-Brown Center on Aging, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.

Abstract

Alzheimer's disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD (3xTg-AD). The effect of lipoic acid, an insulin-mimetic agent, was also investigated to examine its ability in modulating age-dependent metabolic changes. Seven-month-old 3xTg-AD mice were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C nuclear magnetic resonance to determine the concentrations of (13)C-labeled isotopomers of glutamate, glutamine, aspartate, gamma aminobutyric acid, and N-acetylaspartate. An intravenous infusion of [1-(13)C]glucose+[1,2-(13)C]acetate was given for different periods of time to distinguish neuronal and astrocytic metabolism. Enrichments of glutamate, glutamine, and aspartate were calculated after quantifying the total ((12)C+(13)C) concentrations by high-performance liquid chromatography. A hypermetabolic state was clearly evident in 7-month-old 3xTg-AD mice in contrast to the hypometabolic state reported earlier in 13-month-old mice. Hypermetabolism was evidenced by prominent increase of (13)C labeling and enrichment in the 3xTg-AD mice. Lipoic acid feeding to the hypermetabolic 3xTg-AD mice brought the metabolic parameters to the levels of nonTg mice.

PMID:
25099753
PMCID:
PMC4269751
DOI:
10.1038/jcbfm.2014.137
[Indexed for MEDLINE]
Free PMC Article

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