Mitochondrial Disease: Neuronal Defects in Cell Culture

线粒体基因组（mtDNA）缺陷是临床上重要的神经系统疾病的重要原因。 疾病尽管这种认识和线粒体基因组的小尺寸， 机制仍然不确定。因此，尽管诊断是可能的，但临床医生很难提供更多的信息。 对患者的帮助有限。该项目旨在阐明mtDNA突变与 第一次，通过对近端神经系统进行彻底检查， 神经元自身的缺陷。这将通过创造线粒体胞质杂交体来完成， 人、成人来源的胚胎癌细胞（不是胚胎干细胞），从而建立一种 人源性培养神经元中线粒体疾病的模型系统。的细胞缺陷， 神经元将通过分析发育，神经递质表达，电生理学， 细胞死亡敏感性和神经元的生物能量学。希望，在特定缺陷的知识， 细胞水平将允许更好地靶向治疗线粒体呼吸链疾病。

Defects in the mitochondrial genome (mtDNA) are a significant cause of clinically important neurological disease. Despite this recognition and the small size of the mitochondrial genome, the underlying disease mechanisms remain uncertain. Thus, though diagnosis is possible, it is difficult for clinicians to offer more than limited help to patients. This project aims to elucidate the connection between a mtDNA mutation and the resulting neurological disorder by undertaking, for the first time, a thorough examination of the proximal defects occurring within the neurons themselves. This will be done by creating transmitochondrial cybrids in human, adult-derived embryonal carcinoma cells (not embryonicstem cells) and thereby establishing a model system of mitochondrial disorders in human-derived, cultured neurons. The cellular defects of the neurons will be characterized by analyzing the development, neurotransmitter expression, electrophysiology, cell death sensitivity, and bioenergetics of the neurons. Hopefully, the knowledge of the specific defects at the cellular level will allow better targeting for therapy of disorders of the mitochondrial respiratory chain.