Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray.
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.
Department of Physiology, Kyung Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul, Korea.
Jun-Ho
JH
Lee
Eunjung
E
Ko
Young-Eun
YE
Kim
Ji-Young
JY
Min
Jian
J
Liu
Yangseok
Y
Kim
Minkyu
M
Shin
Moochang
M
Hong
Hyunsu
H
Bae
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic