Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

Wang, Hualong; Lian, Kaoqi; Han, Bing; Wang, Yanyong; Kuo, Sheng‐Han; Geng, Yichao; Qiang, Jun; Sun, Miao; Wang, Mingwei

doi:10.3233/jad-131463

Cited by 46 publications

(38 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Numerous efforts have been made in the last years to identify metabolic failures associated with pathological mechanisms underlying to Alzheimer's disease. To this end, different authors have previously addressed the metabolomic investigation of several mouse models of AD using both brain tissue and blood samples, such as theG APP/PS1 E9 (González-Domínguez et al 2014b;2015a), TASTPM (Hu et al, 2012;, CRND8 (Salek et al, 2010;Lin et al, 2013;Lin et al, 2014), APP/PS1 M146L (Woo et al, 2010;Trushina et al, 2012), APP Tg2576 Lalande et al, 2014) or SAMP8 (Jiang et al, 2008;Wang et al, 2014), among others. Thereby, multiple associations have been described between Alzheimer's disease and metabolic perturbations such as oxidative stress, mitochondrial dysfunction, abnormal lipid metabolism or inflammatory processes.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the most important disturbances could be related to dyshomeostasis of different amino acids, such as altered biosynthesis of phenylalanine, tyrosine and tryptophan (a), and abnormal metabolism of histidine (b), tyrosine (c), alanine, aspartate and glutamate (d), arginine and proline (f), as well as perturbed arachidonic acid metabolism (e). (Hu et al, 2012;, CRND8 (Salek et al, 2010;Lin et al, 2013;Lin et al, 2014), APP/PS1 M146L (Woo et al, 2010;Trushina et al, 2012), APP Tg2576 Lalande et al, 2014) or SAMP8 (Jiang et al, 2008;Wang et al, 2014), among others. Thereby, multiple associations have been described between Alzheimer's disease and metabolic perturbations such as oxidative stress, mitochondrial dysfunction, abnormal lipid metabolism or inflammatory processes.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

et al. 2015

View full text Add to dashboard Cite

Abstract:Inflammation plays a prominent role in the pathogenesis of Alzheimer's disease, affecting both brain and the peripheral system. Thus, modulation of inflammation in animal models of this neurodegenerative disorder may be of great interest to elucidate the pathological mechanisms underlying this inflammatory component. To this end, a metabolomic investigation on a triple transgenic mouse model obtained by crossing the APP/PS1 mice with interleukin-4 knockout mice (a model of impaired immune function) was performed for the first time. Serum samples from transgenic mice and wild type animals were analyzed by direct infusion mass spectrometry followed by multivariate statistics in order to identify altered metabolites. Subsequently, metabolic pathway analysis allowed the elucidation of potential pathological mechanisms associated with the development of Alzheimer-type disorders in response to interleukin-4 deficiency, such as impaired homeostasis of histamine, altered metabolism of amino acids (threonine, aspartate and tyrosine), deregulated urea cycle and increased production of eicosanoids. Therefore, this work demonstrates the potential of this triple transgenic model with modulated immunity for the study of pathological mechanisms associated with inflammation in Alzheimer's disease. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation COMMENTS FOR THE AUTHOR:Reviewer #1: The authors have not included some important requests for clarification to be added to the manuscript by the reviewer therefor another minor revision is required. Abstract still poorly writtenFor example this sentence:Thereby, the investigation of this inflammatory component presents a great potential for the elucidation of pathological mechanisms underlying to disease, the discovery of potential markers of diagnosis and the development of novel therapeutic approaches Abstract was rewritten. Authors commentWe did not use internal standards because we considered that the validation of reproducibility in metabolomic methods is better assessed using QC samples. In this sense, Naz et al. recently described that "although spiking some selected metabolites could give a good approach to the general behaviour of the method, results cannot be assumed for all the components in the sample" (J Chromatogr A 2014;1353:99). Instead, biological QCs show a similar composition to real samples, so they are preferable for validating non-targeted approaches. Thus, "the se of QCs in non-targeted metabolomics analysis can be considered as equivalent to the use of standards in routine target analysis". Reviewer comment: I don't agree with this statement how can you account for a one off issue and internal standards are also in the sample matrix. You need add this justification to the manuscriptInternal standards must present similar physico-chemical properties to the chemical species of interest in the sample. However, metabolomics approaches are not focused on individual compounds, so the use of internal standards in these method...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

et al. 2015

View full text Add to dashboard Cite

show abstract

“…One potential explanation might be altered metabolic processes. Thus, histone acetylation is intimately linked to citrate metabolism (76), which is known to decrease in the aging brain (16,77,78 SAHA administration. SAHA was dissolved in drinking water following a previously published formula (42): 0.67 g of SAHA (Cayman Chemical Co.) was dissolved in 1 l of drinking water containing 18 g of β-cyclodextrin (Sigma-Aldrich, Ref 332607).…”

Section: Discussionmentioning

confidence: 99%

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Benito

Urbanke

Ramachandran

et al. 2015

Journal of Clinical Investigation

161

137

View full text Add to dashboard Cite

show abstract

“…By GC-TOF/MS analysis, phosphorylethanolamine was obviously decreased in APP/PS1 mice compared with C57 mice, implying a defect in lipid metabolism in AD brains [29-31]. As the second largest component of brain phospholipids and a precursor of phosphatidylethanolamine (PE), low-level phosphorylethanolamine usually reflects decreased myelination [32, 33].…”

Section: Discussionmentioning

confidence: 99%

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

Han

Wang

Geng³

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

show abstract

Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

Cited by 46 publications

References 37 publications

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

Contact Info

Product

Resources

About