6533b81ffe1ef96bd127883c

RESEARCH PRODUCT

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

Arnon RosenthalJosé Manuel García VerdugoDavid SulzerYvonne SchmitzHeidi S. PhillipsIsabel FariñasDl Choi-lundbergPablo E. CastilloWei Hsien HoAnne M. RyanMark ArmaniniNatasha ShinskyMary HynesAsa Abeliovich

subject

MaleCalbindinsNeuroscience(all)DopamineDopamine AgentsLong-Term PotentiationPresynaptic TerminalsSynucleinsGene ExpressionGlutamic AcidSubstantia nigraNerve Tissue ProteinsNeurotransmissionMotor ActivityHippocampusSynaptic TransmissionReuptakechemistry.chemical_compoundMiceS100 Calcium Binding Protein GDopamineDopaminergic CellmedicineAnimalsAutoreceptorsAlpha-synucleinMice KnockoutNeuronsGeneral NeuroscienceRab3A GTP-Binding ProteinCorpus Striatumrab3A GTP-Binding Proteinnervous system diseasesMice Inbred C57BLSubstantia NigraAmphetaminechemistrynervous systemalpha-SynucleinCalciumFemaleBeta-synucleinNeuroscienceLocomotionmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2000-03-09
http://www.scopus.com/inward/record.url?eid=2-s2.0-0034077041&partnerID=MN8TOARS