Basic Fibroblast Growth Factor Selectively Increases AMPA‐Receptor Subunit GluR1 Protein Level and Differentially Modulates Ca2+ Responses to AMPA and NMDA in Hippocampal Neurons

Bin Cheng, Katsutoshi Furukawa, Joan A. O'Keefe, Yadong Goodman, Muthoni Kihiko, Thomas Fabian, Mark P. Mattson

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Abstract: The excitatory neurotransmitter glutamate is believed to play important roles in development, synaptic plasticity, and neurodegenerative conditions. Recent studies have shown that neurotrophic factors can modulate neuronal excitability and survival and neurite outgrowth responses to glutamate, but the mechanisms are unknown. The present study tested the hypothesis that neurotrophic factors modulate responses to glutamate by affecting the expression of specific glutamate‐receptor proteins. Exposure of cultured embryonic rat hippocampal cells to basic fibroblast growth factor (bFGF) resulted in a concentration‐dependent increase in levels of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)‐receptor subunit GluR1 protein as determined by western blot, dot‐blot, and immunocytochemical analyses. In contrast, bFGF did not alter levels of GluP2/3, GluR4, or the NMDA‐receptor subunit NR1. Nerve growth factor did not affect GluR1 levels. Calcium‐imaging studies revealed that elevation of [Ca2+]i, resulting from selective AMPA‐receptor activation, was enhanced in bFGF‐pretreated neurons. On the other hand, [Ca2+]i responses to NMDA‐receptor activation were suppressed in bFGF‐treated neurons, consistent with previous studies showing that bFGF can protect neurons against NMDA toxicity. Moreover, neurons pretreated with bFGF were relatively resistant to the toxicities of glutamate and AMPA, both of which were shown to be mediated by NMDA receptors. These data suggest that differential regulation of the expression of specific glutamate‐receptor subunits may be an important mechanism whereby neurotrophic factors modulate activity‐dependent neuronal plasticity and vulnerability to excitotoxicity.

Original languageEnglish
Pages (from-to)2525-2536
Number of pages12
JournalJournal of Neurochemistry
Volume65
Issue number6
DOIs
Publication statusPublished - 1995 Dec

Keywords

  • Excitotoxicity
  • Fura‐2 calcium imaging
  • Glutamate
  • Nerve growth factor
  • Neurotrophic factor
  • N‐Methyl‐d‐aspartate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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