突变FUS小鼠神经肌肉连接处结构和功能性质的早期变化
Marat A Mukhamedyarov1, Aydar N Khabibrakhmanov1, Venera F Khuzakhmetova2
1Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia.
International journal of molecular sciences
|May 27, 2023
概括
在FUS基因的突变导致神经肌肉结 (NMJs) 的早期变化,在老鼠与肌缩性侧面硬化症 (ALS). 这些FUS突变会在疾病发作之前损害神经递质释放和突触囊功能.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 肌缩性侧面硬化症 (ALS) 是一种神经退行性疾病,其特征是运动神经元损失和肌肉缺血.
- FUS基因的突变是已知的ALS的原因,通常与'死后'退行模式有关.
- 神经肌肉结 (NMJs) 对肌肉功能至关重要,它们的早期病理是了解ALS进展的关键.
研究的目的:
- 在ALS症状出现前,在FUS突变的小鼠模型中研究膜NMJs的早期结构和功能变化.
- 阐明FUS突变在突触囊泡动力学和神经递质在NMJ释放中的作用.
主要方法:
- 利用光方法和微电极记录来评估突变FUS小鼠中的NMJ功能.
- 分析了脂质过氧化,脂质标记物和突触前蛋白质水平 (SNAP-25,突触1).
- 在各种刺激频率下测量了神经递质释放,突触囊泡动员,内分细胞和过渡体.
主要成果:
- 早期的迹象包括在突变FUS小鼠中的脂质过氧化和改变的脂质标记物.
- 尽管保留了末端板结构,但观察到增加了前突触蛋白 (SNAP-25,突触蛋白1) .
- 在强烈的神经刺激后,神经递质释放和突触囊内细胞分裂被抑制,这与改变的Ca2+动力学和突触素1水平有关.
结论:
- 在强烈活动期间抑制的突触囊泡外内细胞化,可能是由于膜性质变化,突触素1和Ca2+动力学,是FUS-ALS中NMJ病理的早期指标.
- 这些早期的NMJ功能障碍先于明显的末端板退化,并导致神经肌肉接触失调.
- 这些发现凸显了NMJ功能在FUS相关的ALS早期阶段的重要性.
关键词:
这就是FUS FUS.肌缩侧面硬化症 (ALS) 是一种疾病.异步神经递质释放异步神经递质释放.过渡性的过渡性.终端板块 终端板块 结束板块细胞内症是指内细胞内症.异位细胞形成的表细胞化.神经肌肉结节 (NMJ) 是一个神经肌肉结节.尼古丁乙胆受体 (nAChR) 是一种突触中的突触.突触囊泡中的突触囊泡.更多相关视频
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