title: Effects of exogenous alpha-synuclein on stimulated dopamine overflow in dorsal striatum.
abstract: Alpha-synuclein (α-syn) is mainly a presynaptic protein that has been implicated in Parkinson's disease and various other neurodegenerative disorders. Evidence obtained in knockout mice suggests that α-syn controls plasticity of dopamine (DA) overflow in presynaptic terminals. It is also believed that α-syn spreads and may seed its aggregates from cell to cell. The effects of exogenously applied α-syn on dopaminergic neurotransmission have not been studied. We addressed this issue by microinjecting human α-syn protein into the dorsal striatum of wild-type and α-syn knockout mice and monitoring stimulated DA overflow with constant potential amperometry. The evoked DA overflow was decreased in knockout mice six days after α-syn microinjection. The maximal velocity of DA re-uptake was reduced in both genotypes. Similar results were not seen when the effects of microinjected α-syn were studied immediately after the treatment, but instead there was a trend toward an increase in both stimulated DA overflow and maximal velocity of DA re-uptake. We conclude that locally applied human α-syn affects DA overflow and the effects depend on the presence of endogenous α-syn.
authors.affiliation: University of Eastern Finland, School of Pharmacy, Yliopistonranta 1C, P.O. Box 1627, 70211 Kuopio, Finland. Electronic address: anssi.pelkonen@uef.fi.
authors.forename: Anssi
authors.initials: A
authors.lastname: Pelkonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Kallunki
authors.forename: Leonid
authors.initials: L
authors.lastname: Yavich
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D008845:Microinjections; D009154:Mutation; D011994:Recombinant Proteins / Q000494:pharmacology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D051844:alpha-Synuclein; D004298:Dopamine
keywords: Alpha-synuclein; Constant potential amperometry; DA; DAT; Dopamine overflow; Knockout mice; Microinjection; TH; VMAT2; alpha-synuclein; dopamine; dopamine transporter; tyrosine hydroxylase; vesicular monoamine transporter 2; α-Syn