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Open Access Highly Accessed Research article

Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

Jun-Ho Lee, Eunjung Ko, Young-Eun Kim, Ji-Young Min, Jian Liu, Yangseok Kim, Minkyu Shin, Moochang Hong and Hyunsu Bae*

Author Affiliations

Department of Physiology, College of Oriental Medicine, Kyung Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul 130-701, Korea

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BMC Neuroscience 2010, 11:152  doi:10.1186/1471-2202-11-152

Published: 30 November 2010

Abstract

Background

The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated.

Results

We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced.

Conclusions

These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.