Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study.

TitleReversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study.
Publication TypeJournal Article
Year of Publication2014
AuthorsSancheti H, Kanamori K, Patil I, Brinton RDiaz, Ross BD, Cadenas E
JournalJ Cereb Blood Flow Metab
Date Published2014 Feb
KeywordsAlzheimer Disease, Animals, Aspartic Acid, Biomarkers, Citric Acid Cycle, gamma-Aminobutyric Acid, Glucose, Glutamic Acid, Glutamine, Humans, Mice, Mice, Transgenic, Thioctic Acid, Vitamin B Complex

Alzheimer's disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer's disease to be associated with disturbances in glucose metabolism and the subsequent tricarboxylic acid (TCA) cycle-related metabolites like glutamate (Glu), glutamine (Gln), and N-acetylaspartate (NAA). These metabolites have been viewed as biomarkers by (a) assisting early diagnosis of Alzheimer's disease and (b) evaluating the efficacy of a treatment regimen. In this study, 13-month-old triple transgenic mice (a mouse model of Alzheimer's disease (3xTg-AD)) were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C NMR to determine the concentrations of (13)C-labeled isotopomers of Glu, Gln, aspartate (Asp), GABA, myo-inositol, and NAA. Total ((12)C+(13)C) Glu, Gln, and Asp were quantified by high-performance liquid chromatography to calculate enrichment. Furthermore, we examined the effects of lipoic acid in modulating these metabolites, based on its previously established insulin mimetic effects. Total (13)C labeling and percent enrichment decreased by ∼50% in the 3xTg-AD mice. This hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer's disease.

Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID24220168
PubMed Central IDPMC3915206
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
R01 AG016718 / AG / NIA NIH HHS / United States
P01AG026572 / AG / NIA NIH HHS / United States
R01AG016718 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D