UMMS Affiliation

Brudnick Neuropsychiatric Research Institute, Department of Psychiatry

Publication Date

4-3-2015

Document Type

Article

Disciplines

Genetics and Genomics | Genomics | Mental and Social Health | Psychiatric and Mental Health | Psychiatry | Psychiatry and Psychology

Abstract

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.

Rights and Permissions

Citation: BMC Genomics. 2015 Apr 3;16:262. doi: 10.1186/s12864-015-1431-6. Link to article on publisher's site

DOI of Published Version

10.1186/s12864-015-1431-6

Comments

© 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.

Related Resources

Link to Article in PubMed

Keywords

BALB/cJ, UCMS, Unpredictable chronic mild stress, C57BL/6J, Stress, Ubc

Journal/Book/Conference Title

BMC genomics

PubMed ID

25879669

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