Spermidine-induced improvement of memory involves a cross-talk between protein kinases C and A.

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.