Rapid tumor necrosis factor alpha-induced exocytosis of glutamate receptor 2-lacking AMPA receptors to extrasynaptic plasma membrane potentiates excitotoxicity.

ABSTRACT: The postinjury inflammatory response in the CNS leads to neuronal excitotoxicity. Our previous studies show that a major component of this response, the inflammatory cytokine tumor necrosis factor alpha (TNFalpha), causes a rapid increase in AMPA glutamate receptors (AMPARs) on the plasma membrane of cultured hippocampal neurons. This may potentiate neuron death through an increased vulnerability to AMPAR-dependent excitotoxic stress. Here, we test this hypothesis with an in vitro lactose dehydrogenase death assay and examine in detail the AMPAR surface delivery time course, receptor subtype, and synaptic and extrasynaptic distribution after TNFalpha exposure. These data demonstrate that surface levels of glutamate receptor 2 (GluR2)-lacking Ca2+-permeable AMPARs peak at 15 min after TNFal

SUBMITTER: Leonoudakis D 

PROVIDER: S-EPMC6671833 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature