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, Hyunsu Bae
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.
- DNA microarray analysis of RNA isolated from pretreated rat hippocampus
- Confirmation of the expression of target genes by real time polymerase chain reaction (RT-PCR)
- The role of imipramine in gene expression
- The role of fluoxetine in gene expression
- The role of phenelzine in gene expression
- The role of Nelumbinis Semen in gene expression
- Animal and drug treatment: Fluoxetin, imipramine and phenelzine were obtained from Sigma (St. Louis, MO, USA), and Nelumbinis Semen was purchased from Sun Ten Pharmaceutical (Taipei, Taiwan).
- RNA preparation
- Oligonucleotide chip microarray
- Data analysis
- Real-time RT-PCR analysis
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