Hypermetabolic State in the 7-Month-Old Triple Transgenic Mouse Model of Alzheimer'S Disease and the Effect of Lipoic Acid: A <sup>13</sup>C-NMR Study

Sancheti, Harsh; Patil, Ishan; Kanamori, Keiko; Brinton, Roberta Dı́az; Zhang, Wei; Lin, Ai Ling; Cadenas, Enrique

doi:10.1038/jcbfm.2014.137

Cited by 41 publications

(44 citation statements)

References 40 publications

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“…The initial brain hyperglycolysis could be associated with compensatory activation of existing neurons for lost ones in AD-affected brain regions [20]. Because glucose is the brain’s major energy source, the compensation would metabolize more glucose to maintain neurological function [21]. In this phase, the Aβ overexpression and accidental seizure activity also require more glucose utilization for energy, contributing to the hyperglycolysis.…”

Section: Discussionmentioning

confidence: 99%

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Men

Zhu

et al. 2016

IJMS

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Alzheimer’s disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

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Section: Discussionmentioning

confidence: 99%

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Men

Zhu

et al. 2016

IJMS

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“…Numerous other studies have also associated hypermetabolism with early stages of amyloid pathology in transgenic mouse models of β-amyloidosis [28–31]. Luo et al reported hypermetabolism in young Tg2576 mice, prior to the development of plaques [29].…”

Section: Discussionmentioning

confidence: 99%

Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET

Barron

Takao

Zhang

et al. 2016

J Neuroinflammation

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BackgroundObesity has been identified as a risk factor for cognitive decline and Alzheimer’s disease (AD). The aim of this study was to investigate the effect of obesity on neuroinflammation and cerebral glucose metabolism using PET in a mouse model of β-amyloidosis and determine the relationship between these PET imaging biomarkers, pathogenic changes, and functional outcomes.MethodsThree-month-old C57BL/J6 mice were fed either a standard (control group) or high-fat diet (obese group) for 3 months and intracerebroventricularly infused with vehicle or human beta amyloid 1-42 (Aβ42). We assessed obesity-induced abnormalities in peripheral metabolic indices including adiposity, fasting glucose, and glucose tolerance. Brain glucose metabolism was assessed by 18F-FDG PET, and glial activation was assessed using the translocator protein (TSPO) ligand 11C-PBR-28. TSPO expression was confirmed by immunohistochemistry of brain sections obtained from scanned mice. The association between inflammatory state and 11C-PBR-28 PET signals was characterized by examination of the cytokine expression profile in both the serum and hippocampus by antibody array. Learning and memory performance was assessed in the object recognition task, and anxiety-related behavior was assessed in the elevated plus maze.ResultsObesity combined with Aβ infusion promoted neuroinflammation and cerebral hypermetabolism, and these signals were significant predictors of learning and memory performance in the object recognition task. In vivo TSPO signals were associated with inflammatory markers including CXCL1, CXCL2, CXCL12, CCL3, CCL5, TIMP-1, G-CSF, sICAM-1, and IL-1ra.ConclusionsIn vivo cerebral metabolism and TSPO signals indicate that obesity can accelerate amyloid-induced inflammation and associated cognitive decline.

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“…One explanation could be that Tg AD model mice have an increased metabolism compared with their non-Tg littermates (Knight and others 2013; Knight and others 2012; Morgan and Gordon 2008; Sancheti and others 2014). This change in metabolism could be present since obesity leads to upregulated levels of APP in fat cells (Lee and others 2008) and therefore the high levels of APP and/or Aβ in the Tg mice could positively impact metabolism in fat cells (Freeman and others 2012).…”

Section: Discussionmentioning

confidence: 99%

Dietary composition affects the development of cognitive deficits in WT and Tg AD model mice

Kadish

Kumar

Beitnere

et al. 2016

Experimental Gerontology

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Clinical and epidemiological evidence suggests that lifestyle factors, including nutrition, may influence the chances of developing of Alzheimer’s disease (AD), and also likely affect the aging process. Whereas it is clear that high-fat diets are increasing both body weight and the risk of developing Alzheimer’s disease, to date, there have been very few studies comparing diets high with different sources of calories (i.e., high fat versus high protein versus high carbohydrates) to determine whether dietary composition has importance beyond the known effect of high caloric intake to increase body weight, AD pathology and cognitive deficits. In the current study we examined the effects that different diets high in carbohydrate, protein or fat content, but similar in caloric value, have on the development of cognitive impairment and brain pathology in wild-type and Tg AD model mice. The results demonstrate that long term feeding with balanced diets similar in caloric content but with significant changes in the source of calories, all negatively influence cognition compared to the control diet, and that this effect is more pronounced in Tg animals with AD pathology.

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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

Cited by 41 publications

References 40 publications

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET

Dietary composition affects the development of cognitive deficits in WT and Tg AD model mice

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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

Cited by 41 publications

References 40 publications

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET

Dietary composition affects the development of cognitive deficits in WT and Tg AD model mice

Contact Info

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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