NEW INSIGHT ABOUT GHRELIN ?DEPENDENT SYNAPTIC EFFICACY IN HIPPOCAMPUS

Huerta Grande -Cordoba

Congreso; XXVIIICongreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2013

Sociedad Argentina de Investigación en Neurociencia (SAN)

Ghrelin is a 28 amino acid peptide, which is synthesized both peripherally and centrally. The hippocampus is involved in learning and memory processes and it is a brain region that expresses high levels of Ghrelin receptors. Previously, we have shown that intrahippocampal administration of Ghrelin improves memory retention in a dose-dependent manner, and also decreases the threshold to induce Long Term Potentiation (LTP) in this structure, suggesting that Ghrelin could increase neuronal excitability in hippocampus. A critical requirement of glutamate NMDA-receptors containing NR2B-subunits for the LTP induction has been suggested, since ifenprodil, a NR2B-specific antagonist, completely blocks LTP induction in hippocampal slices. Genetic overexpression of NR2B-subunits can lead to an enhanced hippocampal LTP and improved learning and memory. In this work, we combined electrophysiology, evoked glutamate release from synaptosomes, behavioral paradigms, immunohistochemical detection, pharmacological NMDA-receptors blockade and hippocampal cell cultures in order to examine if synaptic efficacy induced by Ghrelin in hippocampus could be related to A) changes in glutamate release from synaptosomes, B) modification in intracellular levels of calcium in cultured pyramidal neurons, C) changes in the expression of the NR2B-containing NMD-receptors. We also study if Ghrelin reverted the cognitive deficit and LTP impairment induced by inhibition of NR2B-containing NMDA-receptors.These results add new insight about the effect of Ghrelin upon the increase of synaptic efficacy in hippocampus, showing the first evidence that Ghrelin increased in about a 30% glutamate-release from synaptosomes as well as raised intracellular calcium release in neurons using Fluo3-AM. In addition, we demonstrated that acute Ghrelin administration induced increases in NR2B-subunit expression, and also reversed the memory deficits and LTP impairment induced by blockade of NR2B-containing NMDA-receptors using the selective antagonist Ro-26181. In conclusion we demonstrated that Ghrelin modulates different pre- and post-synaptic events that could explain the Ghrelin-induced hippocampal plasticity facilitation and memory improvements.Ghrelin; Hippocampus, memory.