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

2017 ◽  
Vol 41 (5) ◽  
pp. 1766-1776 ◽  
Author(s):  
Bing Han ◽  
Jin-Hua Wang ◽  
Yuan Geng ◽  
Li Shen ◽  
Hua-Long Wang ◽  
...  

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.

Amino Acids ◽  
2014 ◽  
Vol 47 (10) ◽  
pp. 2113-2126 ◽  
Author(s):  
Eloy Bejarano ◽  
José Antonio Rodríguez-Navarro

2021 ◽  
Author(s):  
Deyong Zeng ◽  
Jie Cui ◽  
Yishu Yin ◽  
Yi Xiong ◽  
Mengyao Liu ◽  
...  

Abstract BackgroundSpace flight is a special abiotic stress condition. Due to the development of space technology, its potential value has received widespread attention. Space mutation breeding is one of the important methods for human beings to solve food security. However, the molecular mechanism of space mutagenesis is still not very clear.ResultIn this study, two kinds of rice, Dongnong423 (DN3) and Dongnong416 (DN6), were carried on the SJ-10 retractable satellite for 12.5 days in orbit, returned to the ground and planted in the field until the three-leaf (TLP) and tillering stage (TS). The results of antioxidant enzyme activity, soluble sugar, and electron leakage rate revealed that the space environment caused the stress response of rice. The TLP and TS of DN3 identified 113 and 58 different metabolites, respectively. The TLP and TS of DN6 identified 107 and 77 different metabolites, respectively. These metabolites include amino acids, sugars, fatty acids, organic acids and secondary metabolites. We used qRT-PCR technology to explore the changes of enzyme genes in the TCA cycle and amino acid metabolism pathway. Combined with the results of metabolomics, we determined that during the TLP, the TCA cycle rate of DN3 was inhibited and amino acid metabolism was activated, while the TCA cycle rate of DN6 was activated and amino acid metabolism was inhibited. In TS, the TCA cycle rate of DN3 was inhibited, and amino acid metabolism was not significantly changed, while the TCA cycle rate of DN6 was activated and amino acid metabolism was inhibited. These results suggest that the space environment has different stress response mechanisms to the two rice varieties, and these differences may be reflected in energy consumption and compound biosynthesis.ConclusionsThis research uses metabolomics for the first time to explore the effects of space flight team rice. This research provides new insights for further exploring the effects of space biology and space mutation breeding.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 949-949
Author(s):  
Jaspreet Sharma ◽  
Blake Rushing ◽  
Natalia Krupenko ◽  
Susan Sumner ◽  
Sergey Krupenko

Abstract Objectives The goal of the present study was to investigate whether dietary folate restriction exacerbates the metabotype associated with the KO. Methods Hepatic tissues from wildtype (Aldh1l1+/+) and KO (Aldh1l1−/−) mice fed a control (CD), or folate deficient diet (FDD) for 16 weeks were profiled using untargeted metabolomics to identify metabolite changes and affected pathways. Results PCA plots of the 6595 peaks in the preprocessed liver datasets show tight clustering of samples within the groups and clear separation between genotypes, and diets. OPLS-DA analysis showed strong separation between pairwise comparisons of the groups with model statistics (R2X, R2Y, and Q2) all greater than 0.5, indicating that dietary folate and Aldh1l1 alone or in combination have a significant effect on the liver metabolomes in male and female mice. Using MetaboAnalyst for pathway analysis significant differences in bile acid metabolism, nucleotide metabolism, and protein synthesis/amino acid metabolism (aminoacyl-tRNA biosynthesis; alanine, aspartate and glutamate metabolism; valine, leucine and isoleucine biosynthesis) were observed in males. Similarly, in females many perturbations in amino acid metabolism, nucleotide metabolism, carbohydrate metabolism (pyruvate metabolism; fructose and mannose metabolism), sphingolipid metabolism, bile acid metabolism and microbiome metabolism (propanoate metabolism; butanoate metabolism) were noted. Conclusions Dietary folate elicits liver metabolome response depending on Aldh1l1 genotype. Funding Sources NIH, R01


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