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. © 2010 Lee et al; licensee BioMed Central Ltd.

Indexed keywords

EMTREE drug terms: alpha synuclein; amyloid precursor protein; antidepressant agent; caspase 8; cytokine; fluoxetine; gamma interferon; imipramine; iturelix; messenger RNA; Nelumbinis semen extract; phenelzine; plant extract; transforming growth factor beta; unclassified drug; antidepressant agent; tricyclic antidepressant agent

EMTREE medical terms: animal experiment; animal tissue; article; DNA microarray; gene expression profiling; gene identification; genetic analysis; hippocampus; nonhuman; nucleotide sequence; protein metabolism; rat; signal transduction; therapy effect; animal; depression; DNA microarray; drug effect; gene expression profiling; genetic association; genetics; male; metabolism; methodology; Sprague Dawley rat

MeSH: Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Gene Expression Profiling; Genome-Wide Association Study; Hippocampus; Male; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley
Medline is the source for the MeSH terms of this document.

Molecular Sequence Numbers: GENBANK,NM_012596(referenced), NM_012715(referenced), NM_012731(referenced), NM_012750(referenced), NM_012755(referenced), NM_012882(referenced), NM_012910(referenced), NM_017155(referenced), NM_019216(referenced), NM_022617(referenced), NM_030836(referenced), NM_030859(referenced), NM_031131(referenced), NM_031546(referenced), NM_053788(referenced), NM_057149(referenced), NM_138875(referenced)

Chemicals and CAS Registry Numbers: alpha synuclein, 154040-18-3; fluoxetine, 54910-89-3, 56296-78-7, 59333-67-4; gamma interferon, 82115-62-6; imipramine, 113-52-0, 50-49-7; iturelix, 112568-12-4; phenelzine, 156-51-4, 51-71-8;Antidepressive Agents; Antidepressive Agents, Tricyclic