title: Hippocampal PKA/CREB pathway is involved in the improvement of memory induced by spermidine in rats.
abstract: Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor function, and has been reported to facilitate memory formation. In the current study we determined whether or not the PKA/CREB signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the cAMP-dependent protein kinase (PKA) inhibitor, N-[2-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide [H-89, 0.5 ρmol intrahippocampal (ih)] or the antagonist of the NMDA receptor polyamine-binding site (arcaine, 0.02 nmol ih) with SPD (0.2 nmol ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKA and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus 180 min, but not 30 min, after administration, and increased translocation of the catalytic subunit of PKA into the nucleus. Arcaine (0.02 nmol) and H-89 (0.5 ρmol) prevented the stimulatory effect of SPD on PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the PKA/CREB pathways in rats.
authors.affiliation: Department of Chemistry, Center of Exact and Natural Sciences, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Gustavo Petri
authors.initials: GP
authors.lastname: Guerra
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Mello
authors.forename: Guilherme Vargas
authors.initials: GV
authors.lastname: Bochi
authors.forename: Andréia Martini
authors.initials: AM
authors.lastname: Pazini
authors.forename: Roselei
authors.initials: R
authors.lastname: Fachinetto
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Dutra
authors.forename: João Batista
authors.initials: JB
authors.lastname: Calixto
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Maribel Antonello
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001645:Biguanides / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013095:Spermidine / Q000494:pharmacology*
chemical_list: D001645:Biguanides; D017362:Cyclic AMP Response Element-Binding Protein; C006624:arcaine; D017868:Cyclic AMP-Dependent Protein Kinases; D013095:Spermidine