title: Spermidine improves the persistence of reconsolidated fear memory and neural differentiation in vitro: Involvement of BDNF.
abstract: Putrescine, spermidine and spermine are organic cations implicated in learning, memory consolidation, reconsolidation and neurogenesis. These physiological processes are closely related, and convincing evidence indicates that neurogenesis is implicated both, in the establishment and maintenance of remote contextual fear memory. Although brain-derived neurotrophic factor (BDNF) is a key mediator involved in both neurogenesis and memory consolidation, effects of spermidine on persistence of memory after reactivation (reconsolidation) and possible involvement of BDNF have not been investigated. Here, we investigated whether the intrahippocampal infusion of spermidine improves the persistence of reconsolidated contextual fear conditioning memory in rats and whether these possible changes depend on BDNF/TrkB signaling in the hippocampus. The infusion of spermidine immediately and 12h post-reactivation improved fear memory of the animals tested seven but not two days after reactivation. The facilitatory effect of spermidine on the persistence of reconsolidated memory was blocked by the TrkB inhibitor ANA-12 (73.6pmol/site) and accompanied by mature BDNF level increase in the hippocampus, indicating that it depends on the BDNF/TrkB pathway. We also investigated whether spermidine alters BDNF levels and neural progenitor cell differentiation in vitro. Spermidine increased BDNF levels in vitro, facilitating neuritogenesis and neural migration. Spermidine-induced neuritogenesis in vitro was also blocked by ANA-12 (10µM). Since spermidine increases BDNF levels and facilitates neural differentiation in vitro, similar mechanisms may be involved in spermidine-induced facilitation of the persistence of reconsolidated memory.
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Signor
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Bruna Amanda
authors.initials: BA
authors.lastname: Girardi
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Arithane
authors.initials: A
authors.lastname: Lorena Wendel
authors.affiliation: Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 9 7105-900, Brazil.
authors.forename: Pâmella Karina Santana
authors.initials: PKS
authors.lastname: Frühauf
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, 05508-900, Brazil.
authors.forename: Micheli M
authors.initials: MM
authors.lastname: Pillat
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, 05508-900, Brazil.
authors.forename: Henning
authors.initials: H
authors.lastname: Ulrich
authors.affiliation: Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 9 7105-900, Brazil.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS 9 7105-900, Brazil. Electronic address: maribel.rubin@gmail.com.
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D013095:Spermidine / Q000494:pharmacology*
chemical_list: C559317:ANA 12 compound; D001381:Azepines; D001549:Benzamides; D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D013095:Spermidine
keywords: BDNF; Memory; Neural progenitor cells; Persistence of reconsolidation; Polyamines; Spermidine