Netrin-1 improves the amyloid-β-mediated suppression of memory and synaptic plasticity.

Abstract

The aim of this study was to investigate the effects of netrin-1 (NT-1) on amyloid-beta (Aβ)-induced impairments in learning-memory and synaptic plasticity. The NT-1 or its vehicle was administered four times into the Aβ+NT or Aβ+V groups, respectively. The Aβ+SNT group received a single dose of NT-1. The Aβ+HNT group received heat-inactivated NT-1. For the learning-memory and synaptic plasticity assessment, field potentials recording and behavioral experiment were used. Bilateral injection of Aβ1-42 inhibits induction of long-term potentiation (LTP) and decreased memory performance in all the behavioral tasks. However, only by repeated injection of NT-1, significant recovery of LTP and memory was seen. Although, the delivery of HFS to Aβ+NT group recovered EPSP slope of the maintenance phase when compared with Aβ+V, but it failed to recover the induction phase. It can be assumed that NT-1 may have regulatory effects on the synthesis of key proteins and/or structural changes that are responsible for LTP induction, since the protein synthesis and/or structural changes are required for the maintenance phase of LTP.