Gene expression analysis of hypothalamic and hippocampal tissues of rats treated with St. John's wort extract or fluoxetine in a chronic restraint stress model

Hypericum perforatum L., known as St. John's wort (SJW) is indicated as phytotherapeutic agent for the treatment of mild to moderate forms of depression. Data from literature support the hypothesis that chronic stress is a major risk factor for psychiatric illnesses. The aim of the present study was to evaluate the effect of SJW extract (STW3-VI; 250 and 500mg/kg; p.o.) and fluoxetine (10mg/kg, p.o.) on genes involved in the pathogenesis of depression using a chronic restraint stress (CRS) model in rats (1h for 21 consecutive days). Hypothalamic and hippocampal tissues were analyzed using the Affymetrix gene chip Rat Genome 230 2.0 Array, which comprises more than 30,000 rat transcripts. Limma analysis and PANTHER database were used to evaluate the microarray data. Our first results show that chronic stress for 21 days differentially regulated 256 genes in the control group, whereas treatment with fluoxetine in stressed animals influenced 43 genes in the hippocampus. However, in stressed animals treated with 250mg/kg of the SJW extract 140 genes were altered and 223 genes in the 500mg/kg group. In all groups several pathways were identified which provide a link between the various hypotheses of depression. Gene expression profiles for hypothalamic tissues will provide additional information about brain circuits involved in depression.