title: 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.
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.
authors.affiliation: Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Harsh
authors.initials: H
authors.lastname: Sancheti
authors.affiliation: Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Ishan
authors.initials: I
authors.lastname: Patil
authors.affiliation: Enhanced Magnetic Resonance Laboratory, Huntington Medical Research Institutes, Pasadena, California, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kanamori
authors.affiliation: Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Díaz Brinton
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Sanders-Brown Center on Aging, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Lin
authors.affiliation: Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism / Q000494:pharmacology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D002247:Carbon Isotopes; D013549:Sweetening Agents; D014803:Vitamin B Complex; D008063:Thioctic Acid; D005947:Glucose
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