Graduation Program in Biological Sciences: Toxicologic Biochemistry, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
J Neurochem. 2012 Jul;122(2):363-73. doi: 10.1111/j.1471-4159.2012.07778.x. Epub 2012 May 24.
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.
亚精胺（SPD）是一种具有多阳离子结构的内源性脂肪族胺，可调节 NMDA 受体活性并改善记忆。最近的证据表明，cAMP 依赖性蛋白激酶（PKA）和 cAMP 反应元件结合蛋白（CREB）在 SPD 诱导的记忆改善中发挥作用。在本研究中，我们确定钙依赖性蛋白激酶（PKC）信号通路是否参与 SPD 诱导的成年大鼠抑制性回避任务记忆的改善。PKC 抑制剂 3-[1-（二甲基氨基丙基）吲哚-3-基]-4-（吲哚-3-基）马来酰亚胺盐酸盐[GF 109203X，2.5 ρmol，海马内（ih）]与 SPD（0.2 nmol，ih）一起在训练后给药，可防止 SPD 诱导的记忆改善。SPD（0.2 nmol）给药后 30 分钟，海马内给药可促进 PKC 磷酸化。GF 109203X 不仅阻止了 SPD 对 PKC 的刺激作用，还阻止了 PKA 和 CREB 的磷酸化。这些结果表明，在大鼠中，ih 给予 SPD 诱导的记忆增强涉及 PKC 和 PKA/CREB 之间的串扰，伴随着 PKC 和 PKA/CREB 途径的顺序激活。
