在谷氨酸突触信号传递中的AMPK和mTOR交叉声的计算建模
1Chemical Engineering Graduate Program, University of California San Diego, La Jolla, CA, USA.
NPJ systems biology and applications
|July 17, 2023
概括
高频谷氨酸刺激 (>10 Hz) 通过扰乱AMP-激活蛋白激酶 (AMPK) 和哺乳动物目标的拉巴胺素 (mTOR) 振荡,显著改变神经元能量代谢,影响突触可塑性.
科学领域:
- 神经科学是一个神经科学.
- 计算生物学 计算生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 神经元的能量消耗对大脑功能至关重要,突触是主要的能量消耗者.
- 信号传输是突触传输和神经元活动的核心.
- AMP-激活蛋白激酶 (AMPK) 和哺乳动物目标拉巴胺素 (mTOR) 是细胞代谢和命运的关键调节者.
研究的目的:
- 开发一个突触信号的计算模型.
- 调查谷氨酸刺激频率对AMPK和mTOR动态的影响.
- 探索胰岛素信号传递,信号传递和AMPK和mTOR的代谢调节之间的相互作用.
主要方法:
- 开发一个模拟突触信号通路的计算模型.
- 分析AMP-激活蛋白激酶 (AMPK) 和哺乳动物目标的拉巴胺素 (mTOR) 在不同的谷氨酸刺激频率下的振荡.
- 研究胰岛素受体和信号通路之间的交叉声.
主要成果:
- 超过10 Hz的谷氨酸刺激频率会导致AMPK和mTOR振荡的显著扰动 (高达36%).
- 高频刺激使AMPK和mTOR激活曲线下的面积 (AUC) 变化5%.
- 该模型预测AMPK和mTOR激活的多稳定性,受胰岛素信号强度和代谢消耗率的影响.
结论:
- 神经元对谷氨酸刺激频率的代谢反应是不同的,可能会影响突触可塑性.
- 胰岛素和信号通路表现出影响神经元代谢的复杂相互作用.
- 这些发现提高了对神经元代谢,突触修剪和可塑性的理解.
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