cDNA gene expression profile of rat hippocampus after chronic treatment with antidepressant drugs

被引:41
作者
Drigues, N
Poltyrev, T
Bejar, C
Weinstock, M
Youdim, MBH [1 ]
机构
[1] Technion Israel Inst Technol, Fac Med, Eve Topf & Natl Parkinson Fdn Ctr Excellence Neur, Haifa, Israel
[2] Technion Israel Inst Technol, Fac Med, Dept Pharmacol, Haifa, Israel
[3] Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol, Jerusalem, Israel
关键词
depressive disorder; antidepressant; gene expression profiling; oligonucleotide array sequence analysis; hippocampus; rat;
D O I
10.1007/s00702-003-0077-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background. Chronic antidepressant treatment causes alterations in several hippocampal genes, which participate in neuronal plasticity. However the full picture of their mechanism of action is not known. The advent of genomics enables to identify a broader mechanism of action and identify novel targets for antidepressant development. Methods. The present study examined the cDNA microarray gene expression profile in the hippocampus induced by chronic antidepressant treatment, in rats exposed to the forced swim test. Animals were treated for 2 weeks with moclobemide, clorgyline and amitriptyline. Results. The three antidepressants significantly reduced immobility in the forced swim test and initiated significant homologous changes in gene expressions. These include up regulation of cAMP response element binding protein and down regulation of corticotrophin releasing hormone. Other gene changes noted were those related to neuropeptides, neurogenesis and synaptogenesis, including synaptophysin and neogenin. Some 89 genes were changed by at least 2 drugs, out of which 53 were changed oppositely by forced swim test. Confirmation of gene changes, have come from real time RT-PCR. Conclusions. A significant number and homology in gene expression were observed with the three antidepressants. Many of the genes were associated with neurogenesis and synaptogenesis, including synaptophysin and neogenin.
引用
收藏
页码:1413 / 1436
页数:24
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