Abstract
alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.
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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Amphetamine / pharmacology
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Animals
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Autoreceptors / physiology
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Calbindins
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Calcium / pharmacokinetics
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Corpus Striatum / chemistry
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Corpus Striatum / cytology
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Corpus Striatum / physiopathology*
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Dopamine / analysis
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Dopamine / metabolism*
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Dopamine Agents / pharmacology
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Female
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Gene Expression / physiology
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Glutamic Acid / physiology
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Hippocampus / chemistry
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Hippocampus / cytology
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Hippocampus / physiology
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Locomotion / drug effects
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Locomotion / genetics
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Long-Term Potentiation / physiology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Motor Activity / drug effects
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Motor Activity / genetics
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Nerve Tissue Proteins / genetics*
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Neurons / chemistry
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Neurons / physiology
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Presynaptic Terminals / chemistry
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Presynaptic Terminals / metabolism
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S100 Calcium Binding Protein G / analysis
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Substantia Nigra / chemistry
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Substantia Nigra / cytology
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Substantia Nigra / physiopathology*
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Synaptic Transmission / physiology
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Synucleins
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alpha-Synuclein
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rab3A GTP-Binding Protein / genetics
Substances
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Autoreceptors
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Calbindins
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Dopamine Agents
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Nerve Tissue Proteins
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S100 Calcium Binding Protein G
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Snca protein, mouse
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Synucleins
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alpha-Synuclein
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Glutamic Acid
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Amphetamine
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rab3A GTP-Binding Protein
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Calcium
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Dopamine