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Shared changes in gene expression in frontal cortex of four genetically modified mouse models of depression
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Hoyle, D., Juhasz, G., Aso, E., Chase, D., del Rio, J., Fabre, V., Hamon, M., Lanfumey, L., Lesch, K.-P., Maldonado, R., Serra, M.-A., Sharp, T., Tordera, R., Toro, Carla T. and Deakin, J. F. W. (2011) Shared changes in gene expression in frontal cortex of four genetically modified mouse models of depression. European Neuropsychopharmacology, 21 (1). pp. 3-10. doi:10.1016/j.euroneuro.2010.09.011 ISSN 0924-977X.
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Official URL: http://dx.doi.org/10.1016/j.euroneuro.2010.09.011
Abstract
This study aimed to identify whether genetic manipulation of four systems implicated in the pathogenesis of depression converge on shared molecular processes underpinning depression-like behaviour in mice. Altered 5HT function was modelled using the 5-HT transporter knock out mouse, impaired glucocorticoid receptor (GR) function using an antisense-induced knock down mouse, disrupted glutamate function using a heterozygous KO of the vesicular glutamate transporter 1 gene, and impaired cannabinoid signalling using the cannabinoid 1 receptor KO mouse. All 4 four genetically modified mice were previously shown to show exaggerated helpless behaviour compared to wild-type controls and variable degrees of anxiety and anhedonic behaviour. mRNA was extracted from frontal cortex and hybridised to Illumina microarrays. Combined contrast analysis was used to identify genes showing different patterns of up- and down-regulation across the 4 models. 1823 genes were differentially regulated. They were over-represented in gene ontology categories of metabolism, protein handling and synapse. In each model compared to wild-type mice of the same genetic background, a number of genes showed increased expression changes of >10%, other genes showed decreases in each model. Most of the genes showed mixed effects. Several previous array findings were replicated. The results point to cellular stress and changes in post-synaptic remodelling as final common mechanisms of depression and resilience.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | European Neuropsychopharmacology | ||||||||
Publisher: | Elsevier BV | ||||||||
ISSN: | 0924-977X | ||||||||
Official Date: | January 2011 | ||||||||
Dates: |
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Volume: | 21 | ||||||||
Number: | 1 | ||||||||
Page Range: | pp. 3-10 | ||||||||
DOI: | 10.1016/j.euroneuro.2010.09.011 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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