自闭症风险基因Cul3通过老鼠海马神经元中的caspase-3活性改变神经元形态
Qiang-Qiang Xia1, Anju Singh1, Jing Wang1
1Department of Neurobiology, Marnix E. Heersink School of Medicine & Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, United States.
Frontiers in cellular neuroscience
|May 28, 2024
概括
CUL3基因影响大脑发育,影响神经元结构和抑制性突触形成. 抑制caspase-3部分扭转了这些与自闭症谱系障碍相关的发育神经元变化.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种神经发育障碍,其特点是社会互动缺陷和重复行为.
- CUL3基因与ASD有关,它编码了CULLIN-3,这是一种在神经元中作用不明的ubiquitin联酶复合体中的蛋白质.
研究的目的:
- 调查CUL3删除在早期突触发育中的作用和海马体初级神经元培养中的神经元形态.
- 探索caspase-3在CUL3删除诱导的神经元变化的参与.
主要方法:
- 生成的Cul3淘汰赛 (异合体和同合体) 海马体初级神经元培养.
- 分析了树突复杂性,长度,轴突形成和突触脊柱形态.
- 量化了抑制性 (gephyrin/vGAT) 和刺激性 (vGulT1/PSD95) 的突触点.
- 评估caspase-3水平和神经元细胞活力.
- 使用一种卡斯巴酶-3抑制剂 (Z-DEVD-FMK) 来测试救生效应.
主要成果:
- Cul3 删除显著降低了树突复杂性/长度和轴突形成.
- 突触脊柱密度增加,脊柱体积发生变化.
- 观察到抑制性突触标记物 (gephyrin/vGAT) 的密度和同位分减少.
- Cul3删除增加了酶-3水平,降低了神经元活力,这些效应被酶-3抑制部分逆转.
- 卡斯巴酶-3抑制在很大程度上逆转了形态和抑制性突触变化.
结论:
- CUL3在调节神经元形态,抑制突触形成和细胞活力方面发挥着至关重要的作用.
- 卡斯帕酶-3激活与 Cul3 删除后观察到的细胞和突触缺陷有关.
- 向caspase-3可能为ASD相关的神经功能障碍提供治疗途径.
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