Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice
Individual susceptibility determines the magnitude of stress effects on cognitive function. The hippocampus, a brain region of memory consolidation, is vulnerable to stressful environments, and the impact of stress on hippocampus may determine individual variability in cognitive performance. Therefo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00275/full |
| _version_ | 1819133316210622464 |
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| author | Seung H. Jung Milene L. Brownlow Milene L. Brownlow Matteo Pellegrini Ryan Jankord |
| author_facet | Seung H. Jung Milene L. Brownlow Milene L. Brownlow Matteo Pellegrini Ryan Jankord |
| author_sort | Seung H. Jung |
| collection | DOAJ |
| description | Individual susceptibility determines the magnitude of stress effects on cognitive function. The hippocampus, a brain region of memory consolidation, is vulnerable to stressful environments, and the impact of stress on hippocampus may determine individual variability in cognitive performance. Therefore, the purpose of this study was to define the relationship between the divergence in spatial memory performance under chronically unpredictable stress and an associated transcriptomic alternation in hippocampus, the brain region of spatial memory consolidation. Multiple strains of BXD (B6 × D2) recombinant inbred mice went through a 4-week chronic variable stress (CVS) paradigm, and the Morris water maze (MWM) test was conducted during the last week of CVS to assess hippocampal-dependent spatial memory performance and grouped animals into low and high performing groups based on the cognitive performance. Using hippocampal whole transcriptome RNA-sequencing data, differential expression, PANTHER analysis, WGCNA, Ingenuity's upstream regulator analysis in the Ingenuity Pathway Analysis® and phenotype association analysis were conducted. Our data identified multiple genes and pathways that were significantly associated with chronic stress-associated cognitive modification and the divergence in hippocampal dependent memory performance under chronic stress. Biological pathways associated with memory performance following chronic stress included metabolism, neurotransmitter and receptor regulation, immune response and cellular process. The Ingenuity's upstream regulator analysis identified 247 upstream transcriptional regulators from 16 different molecule types. Transcripts predictive of cognitive performance under high stress included genes that are associated with a high occurrence of Alzheimer's and cognitive impairments (e.g., Ncl, Eno1, Scn9a, Slc19a3, Ncstn, Fos, Eif4h, Copa, etc.). Our results show that the variable effects of chronic stress on the hippocampal transcriptome are related to the ability to complete the MWM task and that the modulations of specific pathways are indicative of hippocampal dependent memory performance. Thus, the divergence in spatial memory performance following chronic stress is related to the unique pattern of gene expression within the hippocampus. |
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| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T09:45:21Z |
| publishDate | 2017-08-01 |
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| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-fc883b3f060a4f4db9941cc350181c352022-12-21T18:30:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-08-011010.3389/fnmol.2017.00275275439Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in MiceSeung H. Jung0Milene L. Brownlow1Milene L. Brownlow2Matteo Pellegrini3Ryan Jankord4Applied Neuroscience, Warfighter Interface Division, 711th Human Performance Wing, Air Force Research LaboratoryWright-Patterson AFB, OH, United StatesApplied Neuroscience, Warfighter Interface Division, 711th Human Performance Wing, Air Force Research LaboratoryWright-Patterson AFB, OH, United StatesResearch Associateship Program, National Research Council, National Academies of ScienceWashington, DC, United StatesDepartment of Molecular, Cell, and Developmental Biology, University of California, Los AngelesLos Angeles, CA, United StatesApplied Neuroscience, Warfighter Interface Division, 711th Human Performance Wing, Air Force Research LaboratoryWright-Patterson AFB, OH, United StatesIndividual susceptibility determines the magnitude of stress effects on cognitive function. The hippocampus, a brain region of memory consolidation, is vulnerable to stressful environments, and the impact of stress on hippocampus may determine individual variability in cognitive performance. Therefore, the purpose of this study was to define the relationship between the divergence in spatial memory performance under chronically unpredictable stress and an associated transcriptomic alternation in hippocampus, the brain region of spatial memory consolidation. Multiple strains of BXD (B6 × D2) recombinant inbred mice went through a 4-week chronic variable stress (CVS) paradigm, and the Morris water maze (MWM) test was conducted during the last week of CVS to assess hippocampal-dependent spatial memory performance and grouped animals into low and high performing groups based on the cognitive performance. Using hippocampal whole transcriptome RNA-sequencing data, differential expression, PANTHER analysis, WGCNA, Ingenuity's upstream regulator analysis in the Ingenuity Pathway Analysis® and phenotype association analysis were conducted. Our data identified multiple genes and pathways that were significantly associated with chronic stress-associated cognitive modification and the divergence in hippocampal dependent memory performance under chronic stress. Biological pathways associated with memory performance following chronic stress included metabolism, neurotransmitter and receptor regulation, immune response and cellular process. The Ingenuity's upstream regulator analysis identified 247 upstream transcriptional regulators from 16 different molecule types. Transcripts predictive of cognitive performance under high stress included genes that are associated with a high occurrence of Alzheimer's and cognitive impairments (e.g., Ncl, Eno1, Scn9a, Slc19a3, Ncstn, Fos, Eif4h, Copa, etc.). Our results show that the variable effects of chronic stress on the hippocampal transcriptome are related to the ability to complete the MWM task and that the modulations of specific pathways are indicative of hippocampal dependent memory performance. Thus, the divergence in spatial memory performance following chronic stress is related to the unique pattern of gene expression within the hippocampus.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00275/fullspatial learningcontextual memorychronic variable stresswhole transcriptomeupstream regulator analysisWGCNA (Weighted Gene Co-expression Network Analyses) |
| spellingShingle | Seung H. Jung Milene L. Brownlow Milene L. Brownlow Matteo Pellegrini Ryan Jankord Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice Frontiers in Molecular Neuroscience spatial learning contextual memory chronic variable stress whole transcriptome upstream regulator analysis WGCNA (Weighted Gene Co-expression Network Analyses) |
| title | Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice |
| title_full | Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice |
| title_fullStr | Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice |
| title_full_unstemmed | Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice |
| title_short | Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice |
| title_sort | divergence in morris water maze based cognitive performance under chronic stress is associated with the hippocampal whole transcriptomic modification in mice |
| topic | spatial learning contextual memory chronic variable stress whole transcriptome upstream regulator analysis WGCNA (Weighted Gene Co-expression Network Analyses) |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00275/full |
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