Inhibiting neuronal alpha-synuclein accumulation caused by oli godendrocytic inclusions

多系统萎缩是一种由α-突触核蛋白在少突胶质细胞和神经元中积聚引起的神经退行性疾病。我们建立了一个转基因小鼠模型，其中人α-突触核蛋白在少突胶质细胞中过表达。我们以前的研究表明，少突胶质细胞α-突触核蛋白包涵体诱导神经元α-突触核蛋白积聚，导致小鼠神经元进行性变性。我们还表明，一个不溶性的复合物的α-突触核蛋白和β-III微管蛋白在微管逐步积累在神经元中。α-突触核蛋白在转基因小鼠神经元的突触前末梢中积累增加，并可能减少神经递质的释放。在本研究中，我们研究了神经元α-突触核蛋白积聚对转基因小鼠突触功能的影响。利用全细胞膜片钳记录，我们证明了转基因小鼠的突触功能障碍，微管解聚剂恢复了转基因小鼠的正常功能。

Multiple system atrophy is a neurodegenerative disease caused by α-synuclein accumulation in oligodendrocytes and neurons. We generated a transgenic mouse model in which human α-synuclein was overexpressed in oligodendrocytes. Our previous studies have revealed that oligodendrocytic α-synuclein inclusions induced neuronal α-synuclein accumulation, resulting in progressive neuronal degeneration in mice. We also demonstrated that an insoluble complex of a-synuclein and ss-III tubulin in microtubules progressively accumulated in neurons. α-Synuclein accumulation is increased in the presynaptic terminals of transgenic mice neurons and may reduce neurotransmitter release. In the present study, we investigated the effects of neuronal α-synuclein accumulation on synaptic function in transgenic mice. Using whole-cell patch-clamp recording, we demonstrated synaptic dysfunction in transgenic mice, and a microtubule depolymerizing agent restored the normal function in transgenic mice.