Stress-regulated genes in the brain of two mouse strains with differential responsiveness to antidepressants

There is increasing evidence that psychiatric disorders like depression derive from the impact of environmental pressure –stress– on genetically susceptible individuals. In these disorders the endocrine system for stress management, the hypothalamus pituitary adrenal gland (HPA) axis, is impaired. Since this axis is regulated from higher brain centres, it is important to study the gene expression profile in these brain areas before and after stress. Here we compare two mouse strains that display different basal anxiety and also differential responsiveness to antidepressants. The animals were stressed and sacrificed 4 or 8h later. Brains were isolated and hippocampus CA3 and hypothalamus PVN tissue was obtained by using the micropuncture technique. RNA was isolated and amplified for microarray analysis. Our results yielded interesting genes, likely involved in neurotransmission and signal transduction, e.g.. At this stage, the expression profiles represent candidate genes which need to be verified on the RNA and protein level using targeted approaches such as in situ hybridisation and/or real time PCR. The evaluation of the expression profile will also use the linguistic tools of text mining programs to eventually arrange the regulated genes into signal transduction networks. Genes with a presumed connection to HPA axis and the regulatory network of corticosteroid receptors, together with genes suspected to be involved in antidepressant action, will be of first interest.