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PMID:10707987
| Citation |
Abeliovich, A, Schmitz, Y, Fariñas, I, Choi-Lundberg, D, Ho, WH, Castillo, PE, Shinsky, N, Verdugo, JM, Armanini, M, Ryan, A, Hynes, M, Phillips, H, Sulzer, D and Rosenthal, A (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239-52 |
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| 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. |
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| Keywords |
Amphetamine/pharmacology; Animals; Autoreceptors/physiology; Calcium/pharmacokinetics; Calcium-Binding Protein, Vitamin D-Dependent/analysis; Corpus Striatum/chemistry; Corpus Striatum/cytology; Corpus Striatum/physiopathology; Dopamine/analysis; Dopamine/metabolism; Dopamine Agents/pharmacology; Female; Gene Expression/physiology; Glutamic Acid/physiology; Hippocampus/chemistry; Hippocampus/cytology; Hippocampus/physiology; Locomotion/drug effects; Locomotion/genetics; Long-Term Potentiation/physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity/drug effects; Motor Activity/genetics; Nerve Tissue Proteins/genetics; Neurons/chemistry; Neurons/physiology; Presynaptic Terminals/chemistry; Presynaptic Terminals/metabolism; Substantia Nigra/chemistry; Substantia Nigra/cytology; Substantia Nigra/physiopathology; Synaptic Transmission/physiology; Synucleins; alpha-Synuclein; rab3A GTP-Binding Protein/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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