Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice

Chen, Shuangqing; Cai, Qing; Shen, Yuying; Wang, Peijun; Teng, Gao‐Jun; Zhang, Wei; Zang, Fengchao

doi:10.1016/j.bbr.2012.07.016

Cited by 50 publications

(51 citation statements)

References 46 publications

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“…Longer escape times during the training phase of the MWM in HFDtreated Tg 2576 mice and sucrose-treated APP/PS1 AD mice are associated with an increased Ab burden (Cao et al, 2007). We found no difference in the escape latencies between NCD AD and HFSTZ AD mice during the training phase of the MWM, suggesting that this task is not sufficiently sensitive to detect an impact of HFSTZ treatment on the hippocampus-dependent learning and memory during the early stage of APP/PS1 mice (Chen et al, 2012). Nesting behavior is considered a goal-directed behavior, and the examination of nest construction can be used to assess behavioral planning and organization for the activity of daily living (Fleming, 2009).…”

Section: Discussioncontrasting

confidence: 54%

Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice

Yeh¹,

Yeh²,

Shie

et al. 2015

Neurobiology of Aging

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Section: Discussioncontrasting

confidence: 54%

Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice

Yeh¹,

Yeh²,

Shie

et al. 2015

Neurobiology of Aging

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“…Previous studies using in vivo proton magnetic resonance spectroscopy ( 1 H MRS) found decreases in N-acetylasparatate and glutamate, and an increase in myo-inositol concentrations in APP/PS1 mice (Chen et al, 2012;Marjanska et al, 2005). Glycolytic pathways involving the Kreb's cycle, and neurotransmitter and amino acid metabolism, were found to be significantly affected in APP/PS1 mouse brain (Trushina et al, 2012).…”

Section: Metabolomics Is the Scientific Investigation Of Chemical Promentioning

confidence: 98%

“…It holds considerable potential as a discovery platform for identifying novel diagnostic biomarkers for AD but also many other neurodegenerative diseases. Metabolomics studies have previously been undertaken in APP/PS1 mice (Chen et al, 2012;GonzalezDominguez et al, 2015a;González-Domínguez et al, 2014;Graham et al, 2013b;Marjanska et al, 2005;Trushina et al, 2012;Yao et al, 2009), however, the majority of these studies (including our own (Graham et al, 2013b)) suffer from limitations commonly befalling many metabolomics investigations conducted to date. The current study was designed having noted earlier approaches to undertake a more robust metabolomics evaluation of this important model of AD.…”

Section: Metabolomics Is the Scientific Investigation Of Chemical Promentioning

confidence: 99%

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

Pan

Nasaruddin

Elliott

et al. 2016

Neurobiology of Aging

108

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The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon the metabolome is still not understood, nor is it known how disturbances change as the disease progresses. For the first time we have profiled longitudinally (6, 8, 10, 12 and 18 months) both the brain and plasma metabolome of APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT mice at 8, 10 and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched chain amino acids and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis was evident in two age groups. AD-like pathology therefore impacts greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

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“…MRS studies have shown reduced Glu levels in a mouse model of Alzheimer’s disease (AD) (Chen et al, 2012b) and in humans with AD (Rupsingh et al, 2011). They have also shown a decrease in combined Glu and Gln (referred to as Glx) in the cingulate cortices and posterior cingulate gyrus of AD patients (Hattori et al 2002; Antuono et al 2001).…”

Section: Introductionmentioning

confidence: 99%

3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging

Nikolova

Stark

2017

Neurobiology of Aging

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The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and Glutamate-Glutamine levels using short echo time magnetic resonance spectroscopy (MRS). Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word recall task and resting state functional connectivity (RSFC). While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults. Collapsed across age, we also discovered a negative relationship between Glx intensity and RSFC between the anterior hippocampus and regions in the subcallosal gyrus, replicating a recent finding by Wagner et al., (2016). These findings demonstrate the possibly utility of Glx in identifying age-related changes in the brain and behavior and provide encouragement that MRS can be useful in predicting age-related decline before any physical abnormalities are present.

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Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice

Cited by 50 publications

References 46 publications

Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice

Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging

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