Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.
Journal:
Neuron 2000 JanAuthors:
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, Rosenthal A
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 exhi
...[more]bit 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.[less]
Mesh Headings:
Amphetamine, Animals, Autoreceptors, Calcium, Calcium-Binding Protein, Vitamin D-Dependent, Corpus Striatum, Dopamine, Dopamine Agents, Female, Gene Expression, Glutamic Acid, Hippocampus, Locomotion, Long-Term Potentiation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Nerve Tissue Proteins, Neurons, Presynaptic Terminals, Substantia Nigra, Synaptic Transmission, Synucleins, alpha-Synuclein, rab3A GTP-Binding Protein