过度的翻译会导致与自闭症相关的突触和行为偏差
Emanuela Santini1, Thu N Huynh, Andrew F MacAskill
1Center for Neural Science, New York University, New York, New York 10003, USA.
Nature
|December 25, 2012
概括
由于真核转化启动因子4E (eIF4E) 的增加,蛋白质合成的改变导致小鼠的自闭症类行为. 抑制这个过程逆转了症状,这表明存在因果关系.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,其特点是社会,沟通和行为缺陷.
- 改变的翻译控制和夸张的蛋白质合成是ASD背后的假设机制.
- 对4q染色体的遗传联系,包括EIF4E基因,已在自闭症患者中观察到.
研究的目的:
- 调查真核转化启动因子4E (eIF4E) 在发展自闭症类行为中的因果作用.
- 探索增加eIF4E水平对小鼠模型中蛋白质合成,突触功能和行为的影响.
主要方法:
- 基因改造小鼠具有增加的eIF4E.E.水平.
- 行为评估以确定与自闭症相关的缺陷 (社会互动,重复性行为).
- 对关键大脑区域的突触功能进行电生理学和生物化学分析.
- 药理干预使用一个卡普依赖转化抑制剂 (4EGI-1).
主要成果:
- 具有eIF4E升高的小鼠表现出过度的上限依赖翻译,并表现出类似自闭症的行为,包括重复行为和社会缺陷.
- 这些行为变化与中间前额叶皮质,体和海马体的突触功能障碍有关.
- 翻译抑制剂4EGI-1的脑内静脉内给药改善了类似自闭症的行为.
结论:
- 由eIF4E水平增加所驱动的过度上限依赖转化是导致ASD的潜在分子机制.
- 这种分子变化导致突触功能障碍和特征性自闭症行为.
- 准上限依赖翻译为自闭症谱系障碍提供了潜在的治疗策略.
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