在人体诱导多能干干细胞中获得的神经网络上的体外电生理学药物测试
Giulia Parodi1, Giorgia Zanini2, Linda Collo2
1Department of Informatics, Bioengineering, Robotics, and Systems Engineering (DIBRIS), University of Genova, Genova, Italy. giulia.parodi@edu.unige.it.
Stem cell research & therapy
|November 17, 2024
概括
人类诱导的多能干细胞衍生神经网络在暴露于离子受体对抗剂时显示出显著的电生理学变化. 这项研究描述了药物对这些药物测试模型中的谷氨酸和GABAergic传播的药物影响.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 使用神经元培养和微电极阵列 (MEA) 的体外模型为药物测试提供了简化的体外样式试验.
- 虽然动物模型中的化学调制效应得到了充分的研究,但人类诱导多能干细胞 (hiPSC) 衍生神经网络中电生理学变化的特征缺乏.
研究的目的:
- 描述药理学操纵对不同配置的hiPSC衍生神经网络的电生理学影响.
- 为了研究电离体谷氨酸和GABA受体对抗剂对神经网络活动的影响.
主要方法:
- 建立了三种hiPSC衍生的神经网络配置:完全谷氨酸性 (100E),75%谷氨酸性/25%GABAergic (75E25I) 和完全GABAergic (100I).
- 适用于NMDA受体 (APV),AMPA受体 (CNQX) 和GABA_A受体 (比库库林,皮克罗托克辛,乙etrazole) 的对抗剂.
主要成果:
- 在所有测试的配置中,APV和CNQX取消了网络爆破并改变了功能连接.
- GABA_A受体对抗剂 (BIC,PTX,PTZ) 增加了发射和爆发活动,并增强了功能连接,特别是在具有抑制成分的网络中.
结论:
- 由hiPSC衍生的神经网络对激发性和抑制性神经传递的药理学调制高度敏感.
- 这些发现代表了利用人类衍生的神经元网络用于先进的药物测试应用的关键一步.
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