TY - JOUR
T1 - Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer's disease and the effect of lipoic acid
T2 - A 13 C-NMR study
AU - Sancheti, Harsh
AU - Patil, Ishan
AU - Kanamori, Keiko
AU - Díaz Brinton, Roberta
AU - Zhang, Wei
AU - Lin, Ai Ling
AU - Cadenas, Enrique
N1 - Publisher Copyright:
© 2014 ISCBFM All rights reserve.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - 13C nuclear magnetic resonance
KW - Alzheimer's disease
KW - [1-13C]glucose metabolism
KW - glutamate isotopomers
KW - hypermetabolism
KW - lipoic acid
UR - http://www.scopus.com/inward/record.url?scp=84922219033&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922219033&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2014.137
DO - 10.1038/jcbfm.2014.137
M3 - Article
C2 - 25099753
AN - SCOPUS:84922219033
SN - 0271-678X
VL - 34
SP - 1749
EP - 1760
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 11
ER -