NMDA-Receptor Activation but Not Ion Flux Is Required for Amyloid-Beta Induced Synaptic Depression

作者：Tamburri Albert; Dudilot Anthony; Licea Sara; Bourgeois Catherine; Boehm Jannic^*

来源：PLos One, 2013, 8(6): e65350.

DOI：10.1371/journal.pone.0065350

Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (A beta) in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the long-term changes caused by A beta rather than analyzing its immediate effects. Here we show that acute perfusion of hippocampal slice cultures with oligomeric A beta depresses synaptic transmission within 20 minutes. This depression is dependent on synaptic stimulation and the activation of NMDA-receptors, but not on NMDA-receptor mediated ion flux. It, therefore, appears that A beta dependent synaptic depression is mediated through a use-dependent metabotropic-like mechanism of the NMDA-receptor, but does not involve NMDA-receptor mediated synaptic transmission, i.e. it is independent of calcium flux through the NMDA-receptor.

• 出版日期2013-6-4