Abstract
We examined enhancement of synaptic transmission by neurotrophins at the presynaptic level. In a synaptosomal preparation, brain-derived neurotrophic factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent synapsin I phosphorylation and acutely facilitated evoked glutamate release. PD98059, used to inhibit MAP kinase activity, markedly decreased synapsin I phosphorylation and concomitantly reduced neurotransmitter release. The stimulation of glutamate release by BDNF was strongly attenuated in mice lacking synapsin I and/or synapsin II. These results indicate a causal link of synapsin phosphorylation via BDNF, TrkB receptors and MAP kinase with downstream facilitation of neurotransmitter release.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / pharmacology*
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Gene Expression Regulation, Enzymologic
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Glutamic Acid / metabolism*
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Neurons / enzymology
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Phosphorylation
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Rats
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Rats, Sprague-Dawley
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Stimulation, Chemical
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Synapsins / genetics
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Synapsins / metabolism*
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Synaptic Transmission / drug effects*
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Synaptic Transmission / physiology*
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Synaptosomes / enzymology
Substances
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Brain-Derived Neurotrophic Factor
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Enzyme Inhibitors
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Flavonoids
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Synapsins
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Glutamic Acid
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one