甲甲酸化学疗法诱导了与化学疗法相关的认知障碍背后的持续性三细胞失调
Erin M Gibson1, Surya Nagaraja1, Alfonso Ocampo1
1Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Cell
|December 12, 2018
概括
化学疗法通过破坏寡细胞前体细胞 (OPC) 和白质而导致长期的神经缺陷. 针对炎症性小质细胞可以预防化疗引起的认知障碍.
科学领域:
- 神经科学
- 癌症学
- 细胞生物学
背景情况:
- 化学疗法经常导致长期的神经缺陷,
- 神经前体细胞和白质功能障碍与化疗相关的神经缺陷有关.
研究的目的:
- 研究化疗对神经前体细胞和白质的影响.
- 确定化疗引起的神经功能障碍的机制.
- 探索缓解化疗相关认知障碍的治疗目标.
主要方法:
- 在人类化疗患者中,有持续的寡细胞细胞衰竭.
- 开发了一种甲基化疗诱导的神经功能障碍的小鼠模型.
- 研究了寡细胞前体细胞 (OPC) 的分化和髓化动态.
- 评估微质细胞和星球细胞在化疗引起的神经缺陷中的作用.
- 评估了微质衰竭的治疗潜力.
主要成果:
- 在小鼠模型中证实了白质OPC的持续耗尽和髓化缺陷.
- 观察到增加但不完整的OPC分化,表明微环境扰乱.
- 鉴定了依赖于炎症性微质细胞的持续激活和随后的星球细胞激活.
- 证明微质枯竭能使微质谱系动态,髓微结构和认知行为正常化.
结论:
- 化疗暴露导致持续的三细胞失调.
- 在化疗相关的神经缺陷中,炎症性微质细胞起着至关重要的作用.
- 针对炎症性微质提供一种潜在的治疗策略, 以预防化疗引起的认知障碍.
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