title: Decreased reuptake of dopamine in the dorsal striatum in the absence of α-synuclein.
abstract: The presynaptic protein alpha-synuclein (α-syn) plays a role in dopaminergic neurotransmission in the nigrostriatal dopaminergic system. Mutations in this protein have been linked to pathogenesis of Parkinson's disease. However, the details of regulation of dopamine homeostasis by α-syn and its molecular targets are generally unknown. We investigated the effect of α-syn deletion on striatal dopaminergic homeostasis. Two α-syn deficient mouse lines, one carrying a spontaneous deletion of α-syn locus and the other a transgenic α-syn knockout, were used in the study. Stimulated and basal extracellular dopamine levels were determined in the dorsal striatum by in vivo voltammetry and in vivo microdialysis, respectively. Dopamine transporter expression was studied by immunohistochemistry. Stimulated dopamine overflow and basal extracellular dopamine levels were higher in mice lacking α-syn with a concomitant decrease in dopamine transporter expression and reuptake in the dorsal striatum. We show that α-syn deletion produces significant adaptive changes in the striatal dopaminergic system via modulation of reuptake.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, P. O. Box 1627, University of Eastern Finland, Kuopio Campus, Kuopio 70211, Finland. heramb.chadchankar@uef.fi
authors.forename: Heramb
authors.initials: H
authors.lastname: Chadchankar
authors.forename: Jouni
authors.initials: J
authors.lastname: Ihalainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Leonid
authors.initials: L
authors.lastname: Yavich
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D051844:alpha-Synuclein / Q000172:deficiency* / Q000235:genetics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D051844:alpha-Synuclein; D004298:Dopamine