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Abnormal TAR DNA-binding protein 43 (TDP-43) inclusion bodies can be detected in the degener-ative neurons of amyotrophic lateral sclerosis. In this study, we induced chronic oxidative stress in-jury by applying malonate to cultured mouse cortical motor neurons. In the later stages of the ma-lonate insult, TDP-43 expression reduced in the nuclei and transferred to the cytoplasm. This was accompanied by neuronal death, mimicking the pathological changes in TDP-43 that are seen in patients with amyotrophic lateral sclerosis. Interestingly, in the early stages of the response to ma-lonate treatment, nuclear TDP-43 expression increased, and neurons remained relatively intact, without inclusion bodies or fragmentation. Therefore, we hypothesized that the increase of nuclear TDP-43 expression might be a pro-survival factor against oxidative stress injury. This hypothesis was confirmed by an in vitro transgenic experiment, in which overexpression of wild type mouse TDP-43 in cultured cortical motor neurons significantly reduced malonate-induced neuronal death. Our findings suggest that the loss of function of TDP-43 is an important cause of neuronal dege-neration, and upregulation of nuclear TDP-43 expression might be neuroprotective in amyotrophic lateral sclerosis.
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神经干细胞向运动神经元分化及移植的研究进展
神经干细胞是神经科学领域研究的热点之一.在体外适当的条件下神经干细胞可诱导分化成运动神经元,如添加生长因子、相关信号分子、或添加从脊髓源性神经胶质细胞提取的特殊培养液和骨骼肌培养液等,定向诱导分化的神经元移植于脑或脊髓的病变部位将成为运动神经元退行性病变的潜在治疗方法.