striatal dopamine transmission is subtly modified in human a53tα-synuclein overexpressing mice纹状体多巴胺传输是人类a53tα-synuclein巧妙地修改overexpressing老鼠.pdf

Striatal Dopamine Transmission Is Subtly Modified in Human A53Ta-Synuclein Overexpressing Mice 1 2 2 1 Nicola J. Platt *, Suzana Gispert , Georg Auburger , Stephanie J. Cragg 1 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 2 Department of Neurology, Goethe University Medical School, Frankfurt, Germany Abstract Mutations in, or elevated dosage of, SNCA, the gene for a-synuclein (a-syn), cause familial Parkinson’s disease (PD). Mouse lines overexpressing the mutant human A53Ta-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of a-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA) signalling. In addition A53Ta-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Ta-syn, and explored whether A53Ta-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Ta-syn- overexpressing mice, at up to 24 months. In A53Ta-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Ta-syn overexpressors, and in particular showed slight deficiency when the