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Downregulation ofCcnd1 and Hes6in rat hippocampus after chronic exposure to the antidepressant paroxetine

McHugh, Patrick C, Rogers, Geraldine R., Glubb, Dylan M., Allington, Melanie D., Hughes, Mark, Joyce, Peter R. and Kennedy, Martin A. (2008) Downregulation ofCcnd1 and Hes6in rat hippocampus after chronic exposure to the antidepressant paroxetine. Acta Neuropsychiatrica, 20 (6). pp. 307-313. ISSN 0924-2708

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Abstract

Objective: The mechanism of action of antidepressant drugs is not fully understood. Application of genomic methods enables the identification of biochemical pathways that are regulated by antidepressants, and this may provide novel clues to the molecular and cellular actions of these drugs. The present study examined gene expression profiles in the hippocampus of rats exposed to chronic antidepressant treatment.

Methods: Animals were treated for 12 days with the selective serotonin reuptake inhibitor paroxetine; then, hippocampal ribonucleic acid was recovered, and changes in gene expression were assessed by microarray analysis.

Results: A total of 160 genes that showed differential expression after paroxetine exposure were identified. Using functional relevance and observed fold change as selection criteria, the expression changes in a subset of these genes were confirmed by quantitative polymerase chain reaction.

Conclusion: Of this subset, only two genes, cyclin D1 (Ccnd1) and hairy and enhancer of split 6 (Hes6), showed robust and consistent changes in expression. Both genes were downregulated by paroxetine, and both have been previously implicated in neurogenesis. Further investigation of these two genes may provide new insight into the mechanism of action of antidepressants.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Sharon Beastall
Date Deposited: 26 Jan 2012 12:02
Last Modified: 26 Jan 2012 12:02
URI: http://eprints.hud.ac.uk/id/eprint/12654

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