Journal article

Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia

Joohyung Lee, Wen-Mei Zhu, Davor Stanic, David I Finkelstein, Marjorie H Horne, Jasmine Henderson, Andrew J Lawrence, Louise O'Connor, Doris Tomas, John Drago, Malcolm K Horne

BRAIN | OXFORD UNIV PRESS | Published : 2008

Abstract

Failed storage capacity, leading to pulsatile delivery of dopamine (DA) in the striatum, is used to explain the emergence of 'wearing off' and dyskinaesia in Parkinson's disease. In this study, we show that surviving DA neurons in 6-OHDA lesioned rats sprout to re-innervate the striatum, and maintain terminal density until approximately 60% of neurons are lost. We demonstrate that DA terminal density correlates with baseline striatal DA concentration ([DA]). Electrochemical and synaptosome studies in 6-OHDA lesioned rats and primates suggest that impaired striatal DA re-uptake and increased DA release from medial forebrain bundle fibres contribute to maintaining striatal DA levels. In lesion..

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