Regulation of N-methyl-D-aspartate-induced toxicity in the neostriatum: a role for metabotropic glutamate receptors?

AUTOR(ES)

Colwell, C S

RESUMO

Glutamate release activates multiple receptors that interact with each other and thus determine the response of the cell. Exploring these interactions is critical to developing an understanding of the functional consequences of synaptic transmission. Activation of metabotropic glutamate receptors (mGluRs) inhibits N-methyl-D-aspartate (NMDA)-evoked responses measured electrophysiologically in neostriatal slices. The present study examines the functional consequences of this regulation using infrared differential interference contrast videomicroscopy to measure and characterize glutamate receptor-induced cell swelling in a neostriatal brain slice preparation. This swelling is, in many cases, a prelude to necrotic cell death and the dye trypan blue was used to confirm that swelling can result in the death of neostriatal cells. Activation of mGluRs by the agonist 1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) inhibited NMDA but not amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-induced swelling. This regulation was cell-type specific as tACPD did not alter NMDA-induced swelling in pyramidal cells of the hippocampus. Importantly, these findings could be extended to in vivo preparations. Pretreatment with tACPD limited the size of lesions and associated behavioral deficits induced by intrastriatal administration of the NMDA receptor agonist quinolinic acid.

Documentos Relacionados

• Bicuculline- and phaclofen-sensitive components of N-methyl-D-aspartate-induced hyperpolarizations in rat dorsolateral septal nucleus neurones.
• Dendritic mRNA Targeting of Jacob and N-Methyl-d-aspartate-induced Nuclear Translocation after Calpain-mediated Proteolysis*
• Direct effects of metabotropic glutamate receptor compounds on native and recombinant N-methyl-d-aspartate receptors
• Activation of the metabotropic glutamate receptor attenuates N-methyl-D-aspartate neurotoxicity in cortical cultures.
• Phorbol 12-Myristate 13-Acetate Potentiation of N-Methyl-d-aspartate-Induced Currents in Primary Cultured Cerebellar Granule Cells Is Mediated by Protein Kinase Cα