Positive modulation of AMPA receptors prevents downregulation of GluR2 expression and activates the Lyn-ERK1/2-CREB Signaling in rat brain ischemia

Quan Guang Zhang, Dong Han, Shu Qun Hu, Chong Li, Chang Zhou Yu, Ran Wang, Guang Yi Zhang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are responsible for excitotoxicity induced by ischemic injury in hippocampal CA1 neurons, whereas the molecular mechanisms responsible for their neurotrophic activities are much less studied. Here, we examined the neuroprotective effect of positive modeulation of AMPARs by coapplication of AMPA with PEPA, an allosteric potentiator of AMPARs. We showed that coapplication of AMPA with PEPA protected hippocampal CA1 neurons from brain ischemia-induced death. Coapplication of AMPA with PEPA could prevent downregulated expression of GluR2 subunit caused by ischemia and increase BDNF expression via Lyn-ERK1/2-CREB signaling. Furthermore, TrkB receptor-mediated PI3K/Akt signal pathway was activated after coapplication of AMPA with PEPA, which was related to MAPK pathway and protected CA1 neurons against ischemic insults through depression of JNK3 activity, release of cytochrome c to cytosol and depression of capase-3 activity. Our results revealed that positive modulation of AMPARs could exert neuroprotective effects and the possible signaling pathways underlied.

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
JournalHippocampus
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Keywords

  • AMPA receptor
  • BDNF
  • Ischemia
  • Lyn kinase
  • TrkB signaling

ASJC Scopus subject areas

  • Cognitive Neuroscience

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