Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains
Authors
Malki, KarimMineur, Yann
Tosto, Maria Grazia
Campbell, James
Karia, Priya
Jumabhoy, Irfan
Sluyter, Frans
Crusio, Wim E.
Schalkwyk, Leonard C.
UMass Chan Affiliations
Brudnick Neuropsychiatric Research Institute, Department of PsychiatryDocument Type
Journal ArticlePublication Date
2015-04-03Keywords
BALB/cJUCMS
Unpredictable chronic mild stress
C57BL/6J
Stress
Ubc
Genetics and Genomics
Genomics
Mental and Social Health
Psychiatric and Mental Health
Psychiatry
Psychiatry and Psychology
Metadata
Show full item recordAbstract
BACKGROUND: BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and C57BL/6J) of both sexes and subjected to either unpredictable chronic mild stress (UCMS) or no stress. Differences were statistically evaluated through supervised and unsupervised linear modelling and using Weighted Gene Coexpression Network Analysis (WGCNA). In order to gain further understanding into mechanisms related to stress response, we cross-validated our results with a parallel study from the GENDEP project using WGCNA in a meta-analysis design. RESULTS: The effects of UCMS are visible through Principal Component Analysis which highlights the stress sensitivity of the BALB/cJ strain. A number of genes and gene networks related to stress response were uncovered including the Creb1 gene. WGCNA and pathway analysis revealed a gene network centered on Nfkb1. Results from the meta-analysis revealed a highly significant gene pathway centred on the Ubiquitin C (Ubc) gene. All pathways uncovered are associated with inflammation and immune response. CONCLUSIONS: The study investigated the molecular mechanisms underlying the response to adverse environment in an animal model using a GxE design. Stress-related differences were visible at the genomic level through PCA analysis highlighting the high sensitivity of BALB/cJ animals to environmental stressors. Several candidate genes and gene networks reported are associated with inflammation and neurogenesis and could serve to inform candidate gene selection in human studies and provide additional insight into the pathology of Major Depressive Disorder.Source
BMC Genomics. 2015 Apr 3;16:262. doi: 10.1186/s12864-015-1431-6. Link to article on publisher's siteDOI
10.1186/s12864-015-1431-6Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39770PubMed ID
25879669Related Resources
Link to Article in PubMedRights
© 2015 Malki et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
ae974a485f413a2113503eed53cd6c53
10.1186/s12864-015-1431-6