Resumo

OBJECTIVE: Early life stress seems to put an individual at a greater risk for many mental disorders, such as depression and posttraumatic stress disorder, which may involve the glutamatergic neurotransmission through different receptors in the hippocampal formation. Several studies in postmorten human brains with depression and animal models have reported that AMPA receptors may underlie the glutamatergic mechanisms in this disorder. The aim of this study was to evaluate the changes on the expression of AMPA receptors, GluR1 and GluR2, induced by maternal separation (MS) in the hippocampal formation. METHODS: Pups (n=10) underwent a daily-3h separation from their mothers from PND1-21 and the controls (n=11) were left undisturbed. On PND21, the rats were housed (4/cage) for 5 weeks when were deeply anaesthetized, perfused with paraformaldehyde 4% and their brains removed. The expression of GluR1 and GluR2 subunits was evaluated by immunohistochemistry (n=6/group). The immunopositive cells (IC) were counted in the hippocampal formation (hippocampus, amygdala and entorhinal cortex) by 3 examiners independently, bilaterally, in 3 sections/rat. The average was compared by Student t-test and the level of significance was set at p<0.05. RESULTS: MS induced a non significant decrease in GluR1-IC in CA3 (12%; p=0.065) and no difference was seen in the hilus of dentate gyrus. However, MS induced a significant decrease in GluR2-IC in CA3 (24%; p=0.001) and a significant increase in the hilus of dentate gyrus (36%, p=0.02). The number of GluR1-IC was significantly decreased in basolateral (30%; p=0.015) and lateral amygdala (29%; p<0.001) and in entorhinal cortex (24%; p=0.001). CONCLUSION: Considering the high calcium permeability of the GluR1 subunit, the decreased expression of this subunit in all areas of the hippocampal formation induced by MS suggest a reduction on the neuronal excitability of the glutamatergic loop involved in the brain stimulation triggered by entorhinal cortex in response to stress. The increased expression of the AMPA subunit impermeable to calcium, GluR2, in the hilus of dentate gyrus supports this conclusion as the dentate gyrus is the first area stimulated by the perforant path from entorhinal cortex in response to stress. Committee on Animal Research and Ethics: CEUA-School of Medicine of Catanduva, 01/08