Comparison of gene expression patterns in cerebral cortex between three different animal models of depression

Abstract

Trabajo presentado al XXX Congreso de la Sociedad Española de Farmacología celebrado en Bilbao del 17 al 19 de septiembre de 2008.Animal models involve a unique tool for the study of the pathophysiology of major depression and the evaluation of the therapeutic efficacy of new antidepressant drugs. However, little is known about the gene expression pattern through the brain in these animal models, and their likely resemblance to what happens in humans suffering major depression. The expression level of approximately 30,000 genes was analysed in cerebral cortex samples from three different rat models of depression: model of acute treatment with reserpine (5 mg/kg i.p.), model of olfactory bulbectomy, and model of chronic treatment with corticosterone (18 mg/kg/day, subcutaneously implanted pellet); and compared with that obtained from respective control animals. Expression analysis was carried out with Affymetrix® GeneChip® technology. Results were assessed with Gene Chip Operating Software (GCOS 1.3. Affymetrix®) and analysed using GeneSpring GX v7.3 (Agilent) and dChip bioinformatic software. Detected changes in gene expression were validated by means of quantitative RT-PCR assays. Ontological analysis of the results revealed that genes showing differential expression in three models (n=6-10 animals per group) are involved in neurochemical pathways related with programmed cell death. However, only two of these genes (Fabp7 and C3) showed differential expression level in all three models. Both genes were validated with RTPCR assays. On the other hand, several of the genes classically related to human major depression were studied, although only HTr2a, NTrk3, Crhr1, Ntrk2 and Crh showed expression changes in at least one of the three animal models. These results were not validated with RT-PCR. The results demonstrate that the three models, in spite of showing differences in their gene expression patterns, share modifications in neuronal signalling pathways (apoptosis and cellular differentiation). Some of the genes classically related with depression are also modified in these animal models. These findings suggest that the corticosterone model is the one which most closely resembles the findings in postmortem human brains of depressed subjects.Supported by the Basque Government, Spanish Ministry of Education and Science (SAF 04/02784 and 04/0941) and Instituto de Salud Carlos III (CIBERsam). L.U. is supported by Juan de la Cierva Programme.Peer Reviewe