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

Abstract：

: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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Colwell CS,Altemus KL,Cepeda C,Levine MS

doi

10.1073/pnas.93.3.1200

subject

Has Abstract

pub_date

1996-02-06 00:00:00

pages

1200-4

issue

3

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

杂志文章

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