SIGNAL TRANSDUCTION OF CRFR1 IS ALTERED IN AN ANIMAL MODEL OF DEPRESSION

L. SIFONIOS; MA. L. CLADOUCHOS; G. FERNÁNDEZ MACEDO; S. WIKINSKI

Huerta Grande, Córdoba, Argentina

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

Sociedad Argentina de Neurociencia y Taller de Neurociencia

Corticotrophin releasing factor (CRF) has been shown elevated in depressive patients as well as in animal models of depression. In the hippocampus, one of the brain structures involved in this pathological condition, it exerts its action mainly through activation of type one CRF receptor (CRFR1). CRF activates, trough its receptor, the MAPK extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the area CA3 of the hippocampus, but not in the dentate gyrus (DG). However, the level of the ERK1/2 signaling under chronic CRF exposition is still unclear. It has been proposed that the signaling produced by the coupling of CRF to CRFR1 would be altered and could be responsible, in part, for depressive symptomatology. The aim of this study was to evaluate the levels of CRFR1 and the activation of ERK1/2 in the hippocampus of rats after 21 days of exposure to the learned helplessness (LH) paradigm. The levels of expression of CRFR1 were measured in CA3 and DG by in situ hybridization using a cRNA digoxigenin-labeled probe synthesized by the in vitro transcription of a rat CRFR1 cDNA subcloned in a vector. The activated form of ERK1/2 (pERK1/2) was measured in the area CA3 by immunofluorescence. The non activated form was also measured to discard differences in the levels of the protein.   We compared three groups: a Control group (C, rats not exposed to stress), a Learned Helplessnes group (LH+, rats that develop the behavioural despair after exposure to stress) and a non Learned Helplessness group (LH-, rats that fail to develop the behavioural despair after exposure to stress). LH+ showed a significant decrease in the mRNA CRFR1 expression versus LH- or C, both in CA3 and in DG (p<0.01). This decrease in the levels of the messenger was accompanied with the decrease in the activation of ERK1/2 in the area CA3 (p<0.05). In DG there was no activation of ERK1/2. We conclude that in animals with a model of chronic depression the MAPK signaling triggered by CRF is reduced and is area specific.   Supported by: PICT 31953, PIP 5870, UBACYT M013 and M073