title: Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Brain Aging and Cognitive Neuroscience Laboratory of Hebei province, Shijiazhuang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Clinical laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hua-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yan-Yong
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China.|Brain Aging and Cognitive Neuroscience Laboratory of Hebei province, Shijiazhuang, China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007657:Ketone Bodies / Q000235:genetics / Q000378:metabolism; D055442:Metabolome; D051379:Mice; D008822:Mice, Transgenic; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000596:Amino Acids; D016564:Amyloid beta-Protein Precursor; D007657:Ketone Bodies; D013107:Sphingolipids
keywords: Alzheimer’s disease; Gas chromatography-mass spectrometry; Metabolomics; Stress response; Transgenic mice