New insight about ghrelin ?dependent synaptic efficacy in hippocampus

MARISA GHERSI,; LAURA GABACH; BUTTELER FLORENCIA; MARIELA F PEREZ; DE BARIOGLIO SR

Córdoba

Congreso; XIV Reunión Nacional y III Encuentro Internacional de la AACC; 2013

AACC

Ghrelin (Ghr) is a 28 amino acid peptide, which is synthesized both peripherally and centrally. It is known that Ghr participates in the modulation of several processes related to energy homeostasis, gastrointestinal functions, anxiety-like behavior and growth hormone releasing activity. This peptide is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In the central nervous system, GHS-Rs are mainly expressed in the hypothalamus, and mediate the orexigenic effects. However, they are also, expressed in extra-hypothalamic structures such as the hippocampus (hp) a structure related to learning and memory. In a previous works we have shown that Ghr administration in rats, either intracerebroventricularly or directly into brain areas such as the hp, amygdala or dorsal raphe nucleus enhances memory consolidation in the step-down test, in a dose-dependent manner. We have also demonstrated that hippocampal administration decreases the threshold to induce long term potentiation (LTP). The main events during memory consolidation coincide with the signaling pathway activated during the LTP induction in hippocampal CA1 and dentate gyrus. They are initiated by glutamate release and activation of glutamate receptors NMDA and AMPA. In the CA1 region of the hp, the opening of NMDAR receptor (NMDAR) seems to be necessary for memory formation. Functional NMDAR complexes are composed of NR1 and NR2 subunits. Both NR2A and NR2B subunits play important roles in LTP and associative learning. It has been suggested a critical requirement of NR2B subunit for the induction of LTP; in addition, Ifenprodil, an NR2B-specific antagonist, completely blocks LTP in hippocampal slices. During aging, a switch from NR2B to NR2A in NMDAR is commonly observed in many brain regions and it may contribute to a reduction in adult brain plasticity.