title: Spermidine-induced improvement of memory involves a cross-talk between protein kinases C and A.
abstract: Spermidine (SPD) is an endogenous aliphatic amine with polycationic structure that modulates NMDA receptor activity and improves memory. Recent evidence suggests that cAMP-dependent protein kinase (PKA) and cAMP response element-binding protein (CREB) play a role in SPD-induced improvement of memory. In the current study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the PKC inhibitor, 3-[1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl)maleimide hydrochloride [GF 109203X, 2.5 ρmol, intrahippocampal (ih)] with SPD (0.2 nmol, ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKC phosphorylation in the hippocampus, 30 min after administration. GF 109203X prevented not only the stimulatory effect of SPD on PKC but also PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the cross-talk between PKC and PKA/CREB, with sequential activation of PKC and PKA/CREB pathways, in rats.
authors.affiliation: Graduation Program in Biological Sciences: Toxicologic Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Guerra
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Bochi
authors.forename: Andréia M
authors.initials: AM
authors.lastname: Pazini
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rosa
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D003720:Densitometry; D006624:Hippocampus; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013095:Spermidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007211:Indoles; D008301:Maleimides; D018697:Nootropic Agents; D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013095:Spermidine