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Investigations of non-NMDA receptor-induced toxicity in serum-free antioxidant-rich primary cultures of murine cerebellar granule cells

journal contribution
posted on 1998-07-01, 00:00 authored by F Y Carroll, Steve Cheung, P M Beart
A culture system was developed whereby murine cerebellar granule cells were grown under serum-free conditions in chemically defined B27-supplemented neurobasal medium plus depolarizing K+ levels, to allow the investigation of the role of agonists at the kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in glutamate-mediated neurotoxicity. Neurones were killed in a concentration-dependent manner by L-glutamate, kainate and its analogues, domoate and 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid, but not by (S)-AMPA or (S)-5-fluorowillardiine. Kainate (60% maximal cell death at 1mM) was markedly more toxic than NMDA (40% maximal cell death at 1mM) and was shown to be the predominant cause of excitatory amino acid-induced toxicity in these cells as the neuronal death induced by KA was attenuated by the non-NMDA antagonist CNQX, but not the AMPA antagonist LY293558. This study suggests that serum-free cultures of cerebellar granule cells in B27-supplemented neurobasal medium provide a valuable model system for investigations of the role of the kainate receptor in excitatory amino acid-induced neurodegeneration.

History

Journal

Neurochemistry international

Volume

33

Issue

1

Pagination

23 - 28

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

0197-0186

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1998, Elsevier Science Ltd.