Decreased reuptake of dopamine in the dorsal striatum in the absence of alpha-synuclein

The presynaptic protein alpha-synuclein (alpha-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 alpha-syn and its molecular targets are generally unknown. We investigated the effect of alpha-syn deletion on striatal dopaminergic homeostasis. Two alpha-syn deficient mouse lines, one carrying a spontaneous deletion of alpha-syn locus and the other a transgenic alpha-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 alpha-syn with a concomitant decrease in dopamine transporter expression and reuptake in the dorsal striatum. We show that alpha-syn deletion produces significant adaptive changes in the striatal dopaminergic system via modulation of reuptake. (C) 2011 Elsevier B.V. All rights reserved.