Fresno Institute of Neuroscience, Fresno, CA 93730, USA.
Department of Medicine and Biomedical Research Institute, NYU Grossman Long Island School of Medicine, Long Island, NY 11501, USA.
Int J Mol Sci. 2023 Sep 23;24(19):14488. doi: 10.3390/ijms241914488.
Although there are many biochemical methods to measure amyloid-β (Aβ)42 concentration, one of the critical issues in the study of the effects of Aβ42 on the nervous system is a simple physiological measurement. The in vitro rat sciatic nerve model is employed and the nerve action potential (NAP) is quantified with different stimuli while exposed to different concentrations of Aβ42. Aβ42 predominantly reduces the NAP amplitude with minimal effects on other parameters except at low stimulus currents and short inter-stimulus intervals. The effects of Aβ42 are significantly concentration-dependent, with a maximum reduction in NAP amplitude at a concentration of 70 nM and smaller effects on the NAP amplitude at higher and lower concentrations. However, even physiologic concentrations in the range of 70 pM did reduce the NAP amplitude. The effects of Aβ42 became maximal 5-8 h after exposure and did not reverse during a 30 min washout period. The in vitro rat sciatic nerve model is sensitive to the effects of physiologic concentrations of Aβ42. These experiments suggest that the effect of Aβ42 is a very complex function of concentration that may be the result of amyloid-related changes in membrane properties or sodium channels.
尽管有许多生化方法可以测量淀粉样蛋白-β（Aβ42）的浓度，但在研究 Aβ42 对神经系统的影响时，一个关键问题是进行简单的生理测量。该研究采用体外大鼠坐骨神经模型，在不同浓度的 Aβ42 作用下，用不同的刺激来量化神经动作电位（NAP）。Aβ42 主要降低 NAP 幅度，除了在低刺激电流和短刺激间隔外，对其他参数几乎没有影响。Aβ42 的作用明显呈浓度依赖性，在 70 nM 浓度下，NAP 幅度最大降低，在较高和较低浓度下，对 NAP 幅度的影响较小。然而，即使在 70 pM 的生理浓度范围内，也会降低 NAP 幅度。Aβ42 的作用在暴露后 5-8 小时达到最大，在 30 分钟的冲洗期间不会逆转。体外大鼠坐骨神经模型对生理浓度的 Aβ42 的作用敏感。这些实验表明，Aβ42 的作用是一个非常复杂的浓度依赖性功能，可能是由于膜性质或钠通道的淀粉样相关变化所致。
