scholarly journals Reversal of Metabolic Deficits by Lipoic Acid in a Triple Transgenic Mouse Model of Alzheimer's Disease: A 13C NMR Study

2013 ◽  
Vol 34 (2) ◽  
pp. 288-296 ◽  
Author(s):  
Harsh Sancheti ◽  
Keiko Kanamori ◽  
Ishan Patil ◽  
Roberta Díaz Brinton ◽  
Brian D Ross ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Mouse Model ◽  
Lipoic Acid ◽  
Ex Vivo ◽  
Tca Cycle ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Nmr Study

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 [1-13C]glucose followed by an ex vivo13C NMR to determine the concentrations of 13C-labeled isotopomers of Glu, Gln, aspartate (Asp), GABA, myo-inositol, and NAA. Total (12C+13C) 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 13C 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.

scholarly journals Sex-specific interactions between procedural and deliberative decision-making systems in a mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Rachel Anderson ◽  
Damyan W. Hart ◽  
Brian Sweis ◽  
Mathew A. Sherman ◽  
Mark J. Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Decision Making ◽  
Mouse Model ◽  
Neural Substrates ◽  
Behavioral Changes ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Accurate Picture ◽  
And Control

AbstractA central question in aging and Alzheimer’s disease (AD) is when and how neural substrates underlying decision-making are altered. Here we show that while APP mice, a commonly used mouse model of AD, were able to learn Restaurant Row, a complex neuroeconomic decision-making task, they were significantly impaired in procedural, habit-forming, aspects of cognition and relied heavily on deliberation when making decisions. Surprisingly, these behavioral changes are associated with amyloid-beta (Aβ) pathology and network remodeling in the striatum, a key brain region involved in procedural cognition. Furthermore, APP mice and control mice relied on distinct sex-specific strategies in this neuroeconomic task. These findings provide foundational pillars to examine how aging and age-related neurodegenerative diseases impact decision-making across sexes. They also highlight the need for complex behavioral tasks that allow for the dissociation of competing neurally-distinct decision-making circuits to get an accurate picture of changes in neurodegenerative models of human disease.

scholarly journals A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 1044
Author(s):  
Robert J. Pawlosky ◽  
Yoshihero Kashiwaya ◽  
M. Todd King ◽  
Richard L. Veech
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Tca Cycle ◽  
Abnormal Behavior ◽  
Control Group ◽  
Brain Glucose ◽  
Model Of Alzheimer’S Disease ◽  
Brain Glucose Utilization ◽  
Ketone Ester

Because of a decreased sensitivity toward insulin, a key regulator of pyruvate dehydrogenase (PDH), Alzheimer’s patients have lower brain glucose utilization with reductions in Tricarboxylic Acid (TCA) cycle metabolites such as citrate, a precursor to n-acetyl-aspartate. In the 3xTgAd mouse model of Alzheimer’s disease (AD), aging mice also demonstrate low brain glucose metabolism. Ketone metabolism can overcome PDH inhibition and restore TCA cycle metabolites, thereby enhancing amino acid biosynthesis. A ketone ester of d-β-hydroxybutyrate was incorporated into a diet (Ket) and fed to 3xTgAd mice. A control group was fed a calorically matched diet (Cho). At 15 months of age, the exploratory and avoidance-related behavior patterns of the mice were evaluated. At 16.5 months of age, the animals were euthanized, and their hippocampi were analyzed for citrate, α-ketoglutarate, and amino acids. In the hippocampi of the Ket-fed mice, there were higher concentrations of citrate and α-ketoglutarate as well as higher concentrations of glutamate, aspartate and n-acetyl-aspartate compared with controls. There were positive associations between (1) concentrations of aspartate and n-acetyl-aspartate (n = 14, R = 0.9327), and (2) α-ketoglutarate and glutamate (n = 14, R = 0.8521) in animals maintained on either diet. Hippocampal n-acetyl-aspartate predicted the outcome of several exploratory and avoidance-related behaviors. Ketosis restored citrate and α-ketoglutarate in the hippocampi of aging mice. Higher concentrations of n-acetyl-aspartate corresponded with greater exploratory activity and reduced avoidance-related behavior.

[P1-135]: DEPRESSION IN A PRECLINICAL MOUSE MODEL OF ALZHEIMER's DISEASE: AN AGE-RELATED HEDONIC DEFICIT

2017 ◽  
Vol 13 (7S_Part_6) ◽  
pp. P293-P294
Author(s):  
Adam Brelsford ◽  
Jasmine Clarkson ◽  
Jessica Hall ◽  
Emma J. Kidd ◽  
Rhian S. Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Age Related
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