Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons
Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons
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DOI：
10.1016/j.bbadis.2015.12.021
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发表时间：
2016-04-01
影响因子：
6.2
通讯作者：
Zona, Cristina
中科院分区：
文献类型：
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作者：
Caioli, Silvia;Candelotti, Elena;Zona, Cristina
L-缬氨酸是一种支链氨基酸 (BCAA)，主要被运动员用作饮食整合剂，并与一些遗传性罕见疾病（例如枫糖浆尿病）有关。这种病理是由支链氨基酸代谢改变引起的，有毒酮酸在组织和体液中积累，从而产生严重的神经系统症状。据报道，在支链氨基酸积累的动物模型中，氧化应激水平和脂质过氧化增加。本研究的目的是分析神经元中高浓度的 BCAA 是否会诱导活性氧 (ROS) 的产生，以及通过进行电生理记录是否会改变神经元的功能特性。我们的结果表明，在原代皮质培养物中，高剂量的缬氨酸会增加 ROS 的产生并引起神经元过度兴奋，因为与未处理的神经元相比，动作电位频率和持续钠电流幅度显着增加。由于黄芩素（一种从黄芩根中提取的黄酮）已被证明是一种具有神经保护作用的强抗氧化剂，因此我们评估了其在长期暴露于 L-缬氨酸的初级皮质神经元中可能的抗氧化活性。皮质神经元与黄芩素的预孵育可防止 ROS 产生，并能够恢复神经元过度兴奋性和持续钠电流的增加，表明 ROS 产生与改变的生理参数之间存在直接相关性。总之，我们的数据表明，高缬氨酸浓度引起的皮质神经元电生理变化是由于 ROS 产生的增加，这表明在摄入 BCAA 饮食整合剂时要非常谨慎。 (C) 2015 Elsevier B.V. 保留所有权利。
L-valine is a branched-chain amino acid (BCAA) largely used as dietary integrator by athletes and involved in some inherited rare diseases such as maple syrup urine disease. This pathology is caused by an altered BCAA metabolism with the accumulation of toxic keto acids in tissues and body fluids with consequent severe neurological symptoms. In animal models of BCAA accumulation, increased oxidative stress levels and lipid peroxidation have been reported. The aim of this study was to analyze both whether high BCAA concentrations in neurons induce reactive oxygen species (ROS) production and whether, by performing electrophysiological recordings, the neuronal functional properties are modified. Our results demonstrate that in primary cortical cultures, a high dose of valine increases ROS production and provokes neuronal hyperexcitability because the action potential frequencies and the persistent sodium current amplitudes increase significantly compared to non-treated neurons. Since Baicalein, a flavone obtained from the Scutellaria root, has been shown to act as a strong antioxidant with neuroprotective effects, we evaluated its possible antioxidant activity in primary cortical neurons chronically exposed to L-valine. The preincubation of cortical neurons with Baicalein prevents the ROS production and is able to revert both the neuronal hyperexcitability and the increase of the persistent sodium current indicating a direct correlation between the ROS production and the altered physiological parameters. In conclusion, our data show that the electrophysiological alterations of cortical neurons elicited by high valine concentration are due to the increase in ROS production, suggesting much caution in the intake of BCAA dietary integrators. (C) 2015 Elsevier B.V. All rights reserved.