Activation of metabotropic glutamate receptor subtype mGluR1 contributes to post-traumatic neuronal injury.

Published

Journal Article

The role of phospholipase C-coupled (group I) metabotropic glutamate receptors (mGluR1 and mGluR5) in post-traumatic neuronal injury was examined using rat in vivo and in vitro models. Traumatic injury to mixed neuronal/glial cultures induced phosphoinositide hydrolysis and caused neuronal death. Pharmacological blockade of group I receptors significantly reduced these effects in vitro and decreased neurological deficits as well as neuronal loss produced by traumatic brain injury in vivo. In contrast, activation of group I receptors by a specific agonist in vitro exacerbated post-traumatic neuronal death in a dose-dependent manner. Antisense oligodeoxynucleotide directed to mGluR1, but not to mGluR5, was neuroprotective in vitro, although each oligodeoxynucleotide reduced the respective receptor-stimulated accumulation of inositol phosphates to a similar degree. Together, these findings suggest that activation of mGluR1 contributes to post-traumatic neuronal injury and that mGluR1 antagonists may have therapeutic potential in brain injury.

Full Text

Duke Authors

Cited Authors

  • Mukhin, A; Fan, L; Faden, AI

Published Date

  • October 1, 1996

Published In

Volume / Issue

  • 16 / 19

Start / End Page

  • 6012 - 6020

PubMed ID

  • 8815884

Pubmed Central ID

  • 8815884

International Standard Serial Number (ISSN)

  • 0270-6474

Language

  • eng

Conference Location

  • United States