Brain gene expression in a novel mouse model of postpartum mood disorder

Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799 and Davies, William ORCID: https://orcid.org/0000-0002-7714-2440 2019. Brain gene expression in a novel mouse model of postpartum mood disorder. Translational Neuroscience 10 (1) , pp. 168-174. 10.1515/tnsci-2019-0030

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Abstract

Background Steroid sulfatase (STS) cleaves sulfate groups from steroid hormones; its expression/activity increases in late pregnancy and into the postpartum period. STS-deficient human and mouse mothers display elevated psychopathology and abnormal behaviour respectively; in mice, these effects can be partially normalised by antipsychotic (ziprasidone) administration. Methodology We compared brain gene expression in new mouse mothers administered the STS inhibitor 667-Coumate, or vehicle; significant changes were followed-up with pathway analysis and quantitative polymerase chain reaction (qPCR). Finally, the effects of combined 667-Coumate and ziprasidone administration on expression of the most robustly differentially-expressed genes were examined. Results Surprisingly, no between-group gene expression changes were detected at a False Discovery Rate (FDR)-corrected p<0.1. 1,081 unique expression changes were detected at p<0.05, two top hits were verified by qPCR, and pathway analysis indicated enrichment of genes involved in olfactory transduction. The expression of Stoml3 and Cyp2g1 was unaffected by ziprasidone administration. Conclusions Postpartum behavioural abnormalities in STS-deficient mothers are likely to be the culmination of many small gene expression changes. Our data are consistent with the idea that olfactory function is key to maternal behaviour in mice, and suggest that aberrant expression of olfactory system genes may underlie abnormal maternal behaviour in STS-deficient women.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Springer Verlag
ISSN:	2081-3856
Funders:	MRC
Date of First Compliant Deposit:	26 June 2019
Date of Acceptance:	26 June 2019
Last Modified:	30 Sep 2023 09:04
URI:	https://orca.cardiff.ac.uk/id/eprint/123760

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