TY - JOUR
T1 - Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system
AU - Abeliovich, Asa
AU - Schmitz, Yvonne
AU - Fariñas, Isabel
AU - Choi-Lundberg, Derek
AU - Ho, Wei Hsien
AU - Castillo, Pablo E.
AU - Shinsky, Natasha
AU - Garcia Verdugo, Jose Manuel
AU - Armanini, Mark
AU - Ryan, Anne
AU - Hynes, Mary
AU - Phillips, Heidi
AU - Sulzer, David
AU - Rosenthal, Arnon
N1 - Funding Information:
We thank E. Berry for preparing the manuscript; Allison Bruce and Jim Ligos for assistance with the graphics; Robert Edwards, Robert Malenka, and Sara Jones for useful suggestions; Sharon Erickson, Mabel Chu, and Lucrece Tom for help with genotyping; Linda Loverro and Margaret Kelly for help with animal care; and Almudena G. Yague for assistance with histology. This work was funded in part by the Parkinson's Disease Foundation and the National Institute on Drug Abuse (Y. S. and D. S.).
PY - 2000/1
Y1 - 2000/1
N2 - 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 Ca2+. 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.
AB - 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 Ca2+. 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.
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U2 - 10.1016/S0896-6273(00)80886-7
DO - 10.1016/S0896-6273(00)80886-7
M3 - Article
C2 - 10707987
AN - SCOPUS:0034077041
SN - 0896-6273
VL - 25
SP - 239
EP - 252
JO - Neuron
JF - Neuron
IS - 1
ER -