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Therapeutic potentials of neural stem cells treated with fluoxetine in Alzheimer's disease

机译:氟西汀治疗神经干细胞在阿尔茨海默氏病中的治疗潜力

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摘要

Recent studies have proposed that chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. However, the effect of antidepressants on fetal neural stem cells (NSCs) has not been well defined. Our study shows the dose-dependent effects of fluoxetine on the proliferation and neural differentiation of NSCs. Fluoxetine, even at nanomolar concentrations, stimulated proliferation of NSCs and increased the number of βIII-tubulin (Tuj 1)- and neural nucleus marker (NeuN)-positive cells, but not glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that fluoxetine can enhance neuronal differentiation. In addition, fluoxetine has protective effects against cell death induced by oligomeric amyloid beta (Aβ 42) peptides. Taken together, these results clearly show that fluoxetine promotes both the proliferation and neuronal differentiation of NSCs and exerts protective effects against Aβ 42-induced cytotoxicities in NSCs, which suggest that the use of fluoxetine is applicable for cell therapy for various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases by its actions in NSCs.
机译:最近的研究表明,抗抑郁药的慢性治疗会增加成年海马的神经发生。但是,抗抑郁药对胎儿神经干细胞(NSC)的作用尚未明确。我们的研究表明氟西汀对NSCs的增殖和神经分化具有剂量依赖性。氟西汀即使在纳摩尔浓度下也能刺激NSC增殖,并增加βIII-微管蛋白(Tuj 1)和神经核标记(NeuN)阳性细胞的数量,但不增加胶质纤维酸性蛋白(GFAP)阳性细胞的数量。这些结果表明氟西汀可以增强神经元分化。此外,氟西汀对由寡聚淀粉样β(Aβ42)肽诱导的细胞死亡具有保护作用。综上所述,这些结果清楚地表明氟西汀促进NSCs的增殖和神经元分化,并且对NSC中Aβ42诱导的细胞毒性具有保护作用,这表明氟西汀的用途适用于各种神经退行性疾病的细胞疗法,例如阿尔茨海默氏病和帕金森氏病在国家安全委员会中的作用。

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