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Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system


Abeliovich, A and Schmitz, Y and Farinas, I and Choi-Lundberg, DL and Ho, WH and Castillo, PE and Shinsky, N and Verdugo, JMG and Armanini, M and Ryan, A and Hynes, M and Phillips, H and Sulzer, D and Rosenthal, A, Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system, Neuron, 25, (1) pp. 239-252. ISSN 0896-6273 (2000) [Refereed Article]

DOI: doi:10.1016/S0896-6273(00)80886-7


α-Synuclein (α-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 α-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 α-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 Ca 2+ . Concurrent with the altered DA release, α-Syn(-1-) mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that α-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Choi-Lundberg, DL (Dr Derek Choi-Lundberg)
ID Code:31416
Year Published:2000
Web of Science® Times Cited:1312
Deposited By:Anatomy and Physiology
Deposited On:2005-03-10
Last Modified:2011-08-04

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