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

被引：6

作者：

McHugh, Patrick C. ^{[1
]}

Rogers, Geraldine R. ^{[1
]}

Glubb, Dylan M. ^{[1
]}

Allington, Melanie D. ^{[1
]}

Hughes, Mark ^{[2
]}

Joyce, Peter R. ^{[3
]}

Kennedy, Martin A. ^{[1
]}

机构：

[1] Univ Otago, Dept Pathol, Christchurch 8011, New Zealand

[2] Genet Factors, Christchurch, New Zealand

[3] Univ Otago, Dept Psychol Med, Christchurch 8011, New Zealand

来源：

ACTA NEUROPSYCHIATRICA | 2008年 / 20卷 / 06期

关键词：

microarray; neurogenesis; pharmacogenomics; paroxetine; selective serotonin reuptake inhibitor; STAT3;

D O I：

10.1111/j.1601-5215.2008.00334.x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

McHugh PC, Rogers GR, Glubb DM, Allington MD, Hughes M, Joyce PR, Kennedy MA. Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine. 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. 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. 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. 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.

引用

页码：307 / 313

页数：7

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