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.

TitleHypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer's disease and the effect of lipoic acid: a 13C-NMR study.
Publication TypeJournal Article
Year of Publication2014
AuthorsSancheti H, Patil I, Kanamori K, Brinton RDiaz, Zhang W, Lin A-L, Cadenas E
JournalJ Cereb Blood Flow Metab
Volume34
Issue11
Pagination1749-60
Date Published2014 Nov
ISSN1559-7016
KeywordsAlzheimer Disease, Animals, Carbon Isotopes, Dietary Supplements, Disease Models, Animal, Glucose, Humans, Magnetic Resonance Spectroscopy, Mice, Mice, Transgenic, Sweetening Agents, Thioctic Acid, Vitamin B Complex
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.

DOI10.1038/jcbfm.2014.137
Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID25099753
PubMed Central IDPMC4269751
Grant ListKL2 TR001118 / TR / NCATS NIH HHS / United States
R01 AG016718 / AG / NIA NIH HHS / United States
UL1 TR001120 / TR / NCATS NIH HHS / United States
K01 AG040164 / AG / NIA NIH HHS / United States
P01 AG026572 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D