Literature DB >> 10707987

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

A Abeliovich1, Y Schmitz, I Fariñas, D Choi-Lundberg, W H Ho, P E Castillo, N Shinsky, J M Verdugo, M Armanini, A Ryan, M Hynes, H Phillips, D Sulzer, A Rosenthal.   

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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Year:  2000        PMID: 10707987     DOI: 10.1016/s0896-6273(00)80886-7

Source DB:  PubMed          Journal:  Neuron        ISSN: 0896-6273            Impact factor:   17.173


  602 in total

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