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Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine

Published online by Cambridge University Press:  24 June 2014

Patrick C. McHugh ,
Geraldine R. Rogers ,
Dylan M. Glubb ,
Melanie D. Allington ,
Mark Hughes ,
Peter R. Joyce  and
Martin A. Kennedy
Patrick C. McHugh
Affiliation:
Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand
Geraldine R. Rogers
Affiliation:
Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand
Dylan M. Glubb
Affiliation:
Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand
Melanie D. Allington
Affiliation:
Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand
Mark Hughes
Affiliation:
Genetics Factors, Riccarton, Christchurch, New Zealand
Peter R. Joyce
Affiliation:
Department of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand
Martin A. Kennedy*
Affiliation:
Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand
*
Associate Professor Martin A. Kennedy, Department of Pathology, University of Otago, Christchurch, PO Box 4345, Christchurch 8011, New Zealand. Tel: (64-3) 364-1222; Fax: (64-3) 364-0009; E-mail: [email protected]
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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.

Keywords

microarrayneurogenesispharmacogenomicsparoxetineselective serotonin reuptake inhibitorSTAT3
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 20 , Issue 6 , December 2008 , pp. 307 - 313
Copyright
Copyright © 2008 Blackwell Munksgaard

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