Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains
BMC Genomics. 2015-04-03; 16(1):
DOI: 10.1186/s12864-015-1431-6
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1. BMC Genomics. 2015 Apr 3;16:262. doi: 10.1186/s12864-015-1431-6.
Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on
hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains.
Malki K(1), Mineur YS(2)(3), Tosto MG(4)(5), Campbell J(6), Karia P(7), Jumabhoy
I(8), Sluyter F(9), Crusio WE(10)(11), Schalkwyk LC(12).
Author information:
(1)MRC SGDP Centre, King’s College London at the Institute of Psychiatry, PO80,
DeCrespigny Park, London, UK. .
(2)Present address: Department of Psychiatry, Yale School of Medicine, New Haven,
USA. .
(3)Brudnick Neuropsychiatric Research Institute, University of Massachusetts
Medical School, Worcester, MA 01604, USA, USA. .
(4)MRC SGDP Centre, King’s College London at the Institute of Psychiatry, PO80,
DeCrespigny Park, London, UK. .
(5)Department of Psychology, Tomsk State University, Tomsk, Russia.
.
(6)The Institute of Cancer Research, London, UK. .
(7)MRC SGDP Centre, King’s College London at the Institute of Psychiatry, PO80,
DeCrespigny Park, London, UK. .
(8)MRC SGDP Centre, King’s College London at the Institute of Psychiatry, PO80,
DeCrespigny Park, London, UK. .
(9)MRC SGDP Centre, King’s College London at the Institute of Psychiatry, PO80,
DeCrespigny Park, London, UK. .
(10)Present address: University of Bordeaux, Institute for Cognitive and
Integrative Neuroscience (INCIA), Bordeaux, France. .
(11)Brudnick Neuropsychiatric Research Institute, University of Massachusetts
Medical School, Worcester, MA 01604, USA, USA. .
(12)School of Biological Sciences, University of Essex, Colchester, UK.
.
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.
DOI: 10.1186/s12864-015-1431-6
PMCID: PMC4412144
PMID: 25879669 [Indexed for MEDLINE]