Spermidine-induced improvement of memory consolidation involves PI3K/Akt signaling pathway

Brain Res Bull. 2020 Nov:164:208-213. doi: 10.1016/j.brainresbull.2020.08.018. Epub 2020 Aug 25.

Abstract

Spermidine (SPD) is an endogenous polyamine that plays a facilitatory role in memory acquisition and consolidation. Memory consolidation occurs immediately after learning and again around 3-6 hours later. Current evidence indicates that the polyamine binding site at the NMDA receptor (NMDAr) mediates the effects of SPD on memory. While NMDAr activation increases brain-derived neurotrophic factor (BDNF) release, no study has investigated whether BDNF-activated signaling pathways, such as the phosphatidylinositol 3-kinase (PI3K)/Akt pathway play a role in SPD-induced improvement of memory consolidation. Therefore, the aim of the current study was to evaluate whether the TrkB receptor and the PI3K/Akt pathway are involved in the facilitatory effect of SPD on memory consolidation. Male Wistar rats were trained in the contextual conditioned fear task. SPD, ANA-12 (TrkB antagonist), and LY294002 (PI3K inhibitor) were administered immediately after training. The animals were tested 24 h after training. We found that SPD improved fear memory consolidation and that both ANA-12 and LY294002 prevented the facilitatory effect of SPD on memory. These results suggest that SPD-induced improvement of memory consolidation involves the activation of the TrkB receptor and PI3K/Akt pathway.

Keywords: Akt; BDNF; Consolidation; Hippocampus; Memory; Polyamines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Conditioning, Psychological / drug effects*
  • Fear / drug effects
  • Male
  • Memory / drug effects
  • Memory Consolidation / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Receptor, trkB / metabolism
  • Signal Transduction / drug effects*
  • Spermidine / pharmacology*

Substances

  • Brain-Derived Neurotrophic Factor
  • Ntrk2 protein, rat
  • Receptor, trkB
  • Proto-Oncogene Proteins c-akt
  • Spermidine