Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice
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 hip...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-03-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/471869 |
| _version_ | 1828971188798357504 |
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| author | Bing Han Jin-Hua Wang Yuan Geng Li Shen Hua-Long Wang Yan-Yong Wang Ming-Wei Wang |
| author_facet | Bing Han Jin-Hua Wang Yuan Geng Li Shen Hua-Long Wang Yan-Yong Wang Ming-Wei Wang |
| author_sort | Bing Han |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T13:04:13Z |
| format | Article |
| id | doaj.art-34419dbd41d84c3f9de80f353163bdd4 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-14T13:04:13Z |
| publishDate | 2017-03-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-34419dbd41d84c3f9de80f353163bdd42022-12-21T23:00:20ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-03-014151766177610.1159/000471869471869Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 MiceBing HanJin-Hua WangYuan GengLi ShenHua-Long WangYan-Yong WangMing-Wei WangBackground/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.http://www.karger.com/Article/FullText/471869Alzheimer’s diseaseStress responseTransgenic miceMetabolomicsGas chromatography-mass spectrometry |
| spellingShingle | Bing Han Jin-Hua Wang Yuan Geng Li Shen Hua-Long Wang Yan-Yong Wang Ming-Wei Wang Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice Cellular Physiology and Biochemistry Alzheimer’s disease Stress response Transgenic mice Metabolomics Gas chromatography-mass spectrometry |
| title | Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice |
| title_full | Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice |
| title_fullStr | Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice |
| title_full_unstemmed | Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice |
| title_short | Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice |
| title_sort | chronic stress contributes to cognitive dysfunction and hippocampal metabolic abnormalities in app ps1 mice |
| topic | Alzheimer’s disease Stress response Transgenic mice Metabolomics Gas chromatography-mass spectrometry |
| url | http://www.karger.com/Article/FullText/471869 |
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