title: Intrahippocampal infusion of spermidine improves memory persistence: Involvement of protein kinase A.
abstract: Spermidine (SPD) is an endogenous aliphatic amine that modulates GluN2B-containing NMDA receptors and improves memory. Recent evidence suggests that systemic SPD improves the persistence of the long term memory of fear. However, the role of hippocampal polyamines and its binding sites in the persistence of fear memory is to be determined, as well as its putative underlying mechanisms. This study investigated whether the intrahippocampal (i.h.) infusion of spermidine or arcaine, modulators of polyamine binding site at GluN2B-containing NMDA receptors, alters the persistence of the memory of contextual fear conditioning task in rats. We also investigated whether protein synthesis and cAMP dependent protein kinase (PKA) play a role in SPD-induced improvement of the fear memory persistence. While 12h post-training infusion of spermidine facilitated, arcaine and the inhibitor of protein synthesis (anisomycin) impaired the memory of fear assessed 7days after training. The infusion of arcaine, anisomycin or a selective PKA inhibitor (H-89), at doses that have no effect on memory per se, prevented the SPD-induced improvement of memory persistence. H-89 prevented the stimulatory effect of SPD on phospho-PKA/total-PKA ratio. These results suggests that the improvement of fear memory persistence induced by spermidine involves GluN2B-containing NMDA receptors, PKA pathway and protein synthesis in rats.
authors.affiliation: Graduation Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Signor
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Temp
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Oliveira
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Bruna A
authors.initials: BA
authors.lastname: Girardi
authors.affiliation: Graduation Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Mayara A
authors.initials: MA
authors.lastname: Gais
authors.affiliation: Graduation Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Vinicius R
authors.initials: VR
authors.lastname: Funck
authors.affiliation: Graduation Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil; Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil. Electronic address: maribel.rubin@gmail.com.
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001645:Biguanides / Q000008:administration & dosage / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects*; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001645:Biguanides; D007546:Isoquinolines; D018697:Nootropic Agents; D011073:Polyamines; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D013449:Sulfonamides; C006624:arcaine; D000841:Anisomycin; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013095:Spermidine
keywords: Fear conditioning; Hippocampus; Memory persistence; Polyamines; Protein kinase A