Signal transduction of CRFR1 is altered in an animal model of depression

FERNÁNDEZ MACEDO, GEORGINA; SIFONIOS L; CLADOUCHÓS, MARÍA LAURA; WIKINSKI S

Huerta Grande, Córdoba

Congreso; First Joint Meeting of the Argentine Society for Neurosciences and the Argentine Workshop in Neurosciences; 2009

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

SIGNAL TRANSDUCTION OF CRFR1 IS ALTERED IN AN ANIMAL MODEL OF DEPRESSION 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 (CRF1). CRF activates, through CRF1, the extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in the area CA3 of the hippocampus. However, the level of the ERK1/2 signaling under chronic CRF exposition is unclear. It has been proposed that the signaling produced by the coupling of CRF to CRF1 would be altered and could be res`ponsible, in part, for the depressive symptomatology. We evaluated the levels of CRF1 and the activation of ERK1/2 (pERK1/2) in the hippocampus of rats after 21 days of exposure to the learned helplessness (LH) paradigm. the levels of expression of CRF1 were measured by ibn sity hybridization using a cRNA digoxigenin-labeled probe. pERK 1/2 was measured by immunofluorescence. The non activated form was also measured to discard differences in the levels of the protein. We compared three groups: C (rats not exposed to stress), LH+  (rats that develo pthe behavioural despair after exposure to stress) and LH-  (rats that fail to develop the behavioural despair after exposure to stress). LH+ showed a decrease in the CRF1 expression versus LH- or C, both in CA3 and in dentate gyrus (p < 0.01). this result was accompanied with the decrease in the activation of ERK 1/2 in the area CA3 (p z 0.05). In the dentate gyrus there was no activation of ERK 1/2. We conclude that in animals with a model of chronic depression the MAPK signaling triggered byu CRF is reduced and is area specific. Supported by: PICT 31953, PIP 5870 and UBACYT M013.