Abstract
1. The expression of brain-derived neurotrophic factor (BDNF) mRNA is induced by neuronal activity through increased intracellular calcium. As BDNF also increases intracellular calcium levels through trkB activation, we have examined here whether BDNF also regulates the synthesis of its own mRNA. 2. Neurotrophin mRNA expression was induced with kainic acid administration in transgenic mice overexpressing the dominant-negative form of BDNF receptor trkB and wild-type littermates. 3. Kainate strongly induced BDNF mRNA expression in both genotypes, but the up-regulation was significantly lower in transgenic mice. 4. These data suggest that the synthesis of BDNF mRNA is at least partly mediated by BDNF release and the activation of trkB receptors. The present findings further suggest that the BDNF signaling system in brain is regulated by positive feedback.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Behavior, Animal / physiology
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Brain / metabolism
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Brain-Derived Neurotrophic Factor / biosynthesis*
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism
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Excitatory Amino Acid Agonists / administration & dosage
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Excitatory Amino Acid Agonists / pharmacology
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Gene Expression Regulation / genetics
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Injections, Intraperitoneal
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Kainic Acid / administration & dosage
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Kainic Acid / pharmacology*
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Male
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Mice
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Mice, Transgenic
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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RNA, Messenger / biosynthesis*
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Receptor, trkB / genetics
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Receptor, trkB / metabolism*
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Receptor, trkB / physiology
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Transgenes / genetics
Substances
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Brain-Derived Neurotrophic Factor
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Excitatory Amino Acid Agonists
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Protein Isoforms
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RNA, Messenger
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Receptor, trkB
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Kainic Acid