Signor Cristiane, Temp Fernanda R, Mello Carlos F, Oliveira Mauro S, Girardi Bruna A, Gais Mayara A, Funck Vinicius R, Rubin Maribel A
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.
Neurobiol Learn Mem. 2016 May;131:18-25. doi: 10.1016/j.nlm.2016.03.003. Epub 2016 Mar 9.
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.
亚精胺（SPD）是一种内源性脂肪胺，可调节含GluN2B的N-甲基-D-天冬氨酸受体（NMDA受体）并改善记忆力。最近的证据表明，全身性亚精胺可改善恐惧长期记忆的持久性。然而，海马多胺及其结合位点在恐惧记忆持久性中的作用以及可能的潜在机制仍有待确定。本研究调查了向大鼠海马内注射亚精胺或阿卡因（含GluN2B的NMDA受体上多胺结合位点的调节剂）是否会改变情境恐惧条件反射任务记忆的持久性。我们还研究了蛋白质合成和环磷酸腺苷依赖性蛋白激酶（PKA）在亚精胺诱导的恐惧记忆持久性改善中是否起作用。训练后12小时注射亚精胺促进了记忆，而阿卡因和蛋白质合成抑制剂（茴香霉素）则损害了训练7天后评估的恐惧记忆。注射对记忆本身无影响剂量的阿卡因、茴香霉素或选择性PKA抑制剂（H-89）可阻止亚精胺诱导的记忆持久性改善。H-89阻止了亚精胺对磷酸化PKA/总PKA比率的刺激作用。这些结果表明，亚精胺诱导的大鼠恐惧记忆持久性改善涉及含GluN2B的NMDA受体、PKA途径和蛋白质合成。
