Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus

Although the hypothalamus has been long considered the main ghrelin (Ghr) target organ mediating orexigenic effects, recently it has been shown that in-vivo Ghr hippocampus administration improves learning and memory in the inhibitory avoidance paradigm. However, the possible mechanisms underlying t...

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Detalles Bibliográficos
Autores: Carlini, Valeria Paola, Perez, Mariela Fernanda, Salde, Estela, Schiöth, Helgi Birgir, Ramirez, Oscar Angel, Rubiales, Susana Elizabeth
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/132244
Acceso en línea:http://hdl.handle.net/11336/132244
Access Level:acceso abierto
Palabra clave:GHRELIN
HIPPOCAMPUS
LONG-TERM POTENTIATION
MEMORY CONSOLIDATION
NITRIC OXIDE SYNTHASE
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario:Although the hypothalamus has been long considered the main ghrelin (Ghr) target organ mediating orexigenic effects, recently it has been shown that in-vivo Ghr hippocampus administration improves learning and memory in the inhibitory avoidance paradigm. However, the possible mechanisms underlying this memory facilitation effect have not been clarified. Given that the biochemical memory cascade into the hippocampus involves nitric oxide (NO) synthesis via NO synthase (NOS) activation, we investigated 1) if Ghr administration modulated NOS activity in the hippocampus; and 2) if hippocampal NOS inhibition influenced Ghr-induced memory facilitation, using a behavioral paradigm, biochemical determinations and an electrophysiological model. Our results showed that intra-hippocampal Ghr administration increased the NOS activity in a dose dependent manner, and reduced the threshold for LTP generation in dentate gyrus of rat hippocampus. Moreover, pre-administration of NG-nitro-. l-arginine (l-NOArg) in the hippocampus partially prevented the Ghr-induced memory improvement, abolished the increase in NOS activity, and prevented the decreased threshold to generate LTP induced by Ghr. These findings suggest that activation of the NOS/NO pathway in hippocampus participates in the effects of Ghr on memory consolidation and is related with plastic properties of the hippocampal three-synaptic loop. © 2010 Elsevier Inc.