Abstract
High KCI or NMDA treatment promotes the survival of cultured neonatal cerebellar granule cells, and these cells become sensitive to NMDA toxicity after prolonged K+ depolarization. Following both treatments, the NMDA receptor increases, as assessed by fura-2 fluorescence analysis of NMDA receptor-mediated intracellular Ca2+ increase. Northern analysis indicates that both treatments specifically up-regulate NMDAR2A subunit mRNA through an increase in resting intracellular Ca2+ concentration. Antisense oligonucleotide analysis further indicates that NMDAR2A mRNA up-regulation is responsible for NMDA receptor induction. Our results demonstrate that regulation of a specific NMDA receptor subunit mRNA governs NMDA receptor induction, which is thought to play an important role in granule cell survival and death.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Base Sequence
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Blotting, Northern
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / metabolism*
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Gene Expression / drug effects
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Gene Expression / physiology*
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Macromolecular Substances
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Molecular Sequence Data
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N-Methylaspartate / pharmacology*
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N-Methylaspartate / toxicity
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Oligonucleotides, Antisense
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Potassium / pharmacology*
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RNA, Messenger / biosynthesis*
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / biosynthesis*
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Receptors, N-Methyl-D-Aspartate / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology
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Up-Regulation / drug effects
Substances
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Macromolecular Substances
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Oligonucleotides, Antisense
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RNA, Messenger
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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Potassium