University of Eastern Finland, School of Pharmacy, Yliopistonranta 1C, P.O. Box 1627, 70211 Kuopio, Finland.
Neurosci Lett. 2013 Oct 25;554:141-5. doi: 10.1016/j.neulet.2013.08.072. Epub 2013 Sep 8.
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.
α-突触核蛋白（α-syn）主要是一种突触前蛋白，与帕金森病和各种其他神经退行性疾病有关。敲除小鼠获得的证据表明，α-syn 控制多巴胺（DA）在突触前末梢溢出的可塑性。人们还认为，α-syn 会扩散，并可能将其聚集体从一个细胞传播到另一个细胞。尚未研究外源性应用的 α-syn 对多巴胺能神经传递的影响。我们通过将人 α-syn 蛋白微注射到野生型和 α-syn 敲除小鼠的背侧纹状体中来解决这个问题，并通过恒电位安培法监测刺激的 DA 溢出。α-syn 微注射六天后，敲除小鼠的诱发性 DA 溢出减少。两种基因型的 DA 再摄取最大速度均降低。在处理后立即研究微注射的 α-syn 的影响时，并未出现类似的结果，而是刺激的 DA 溢出和 DA 再摄取最大速度均有增加的趋势。我们得出的结论是，局部应用的人 α-syn 会影响 DA 的溢出，并且这种影响取决于内源性 α-syn 的存在。
