极低频电磁场通过改善突触功能治疗阿尔兹海默病的作用及机制研究

Alzheimer’s disease (AD) is characterized by a progressive decline in cognitive and memory function, which is the most frequent form of dementia in the elderly. However, no effective drug and treatment is currently available. It is acknowledged that synaptic plasticity plays a crucial role in the process of learning and memory. Besides, it is showed that down-regulation of N-methyl-D-aspartate (NMDA) receptors and reduction of long term potentiation resulted in synapic dysfunction, which finally caused AD. Interestingly, our previous study showed that exposure to 500μT/50Hz extremely low frequency electromagnetic fields (ELF EMF) ameliorated AD in mice by improving the cognitive and memory function. Meanwhile, we also showed that ELF EMF exposure up-regulated the expression of NMDA receptors. Thus, we hypothesized that exposure to ELF EMF could up-regulate the expression of NMDA receptors, and improve the synaptic function, which finally ameliorated AD. In order to prove the hypothesis, we constructed the ELF EMF exposure device by our own, and used the APP/PS1/Tau transgenic mice as the model, which developed to AD spontaneously. In the present study, we are going to figure out the threshold and the optimal intensity of ELF EMF in the mitigation of AD, as well as the underlying mechanism.

阿尔兹海默病（AD）是一种以认知和记忆功能持续减退为主要临床表现的疾病。截至目前，AD的治疗仍缺乏有效的药物和手段。突触可塑性被认为是学习和记忆的神经生物学基础。有研究表明，N-甲基-D-天冬氨酸（NMDA）受体表达下降、长时程增强减弱是导致突触功能减退，进而导致AD的主要发病机制。有意思的是，我们前期研究结果显示，500μT/50Hz 极低频电磁场（ELF EMF）暴露可以明显改善小鼠的记忆和认知功能，延缓AD的发生。前期研究结果还表明，ELF EMF暴露可以上调NMDA受体表达。因此我们推测，ELF EMF暴露可以通过上调NMDA受体表达，改善突触功能，并最终达到治疗AD的目的。为了验证我们的假设，我们采用自发发生AD的转基因小鼠为研究对象，并采用自主研发的ELF EMF暴露装置进行干预，研究ELF EMF暴露对AD的治疗作用，明确其有效治疗阈值及最佳治疗强度，并深入研究其作用机制。

阿尔兹海默病（AD）是一种以认知和记忆功能持续减退为主要临床表现的疾病。然而截至目前,仍缺乏有效的治疗药物和手段。突触可塑性被认为是学习和记忆的神经生物学基础。有研究表明，N-甲基-D-天冬氨酸（NMDA）受体表达下降、长时程增强（LTP）减弱是导致突触功能减退，进而导致AD的主要发病机制。本项目组以自主设计研发的暴露装置为工具，研究观察到500μT/50Hz 极低频电磁场（ELF EMF）暴露可以明显改善神经元的氧化应激和凋亡水平，上调NMDA受体表达，改善突触树突棘生发能力，增强神经元LTP水平，进而改善AD小鼠的记忆和认知功能，缓解AD的发生。这其中，500μT组可能发挥着更好的效果。因此，本研究证实ELF EMF对AD的治疗作用，并探讨了其中机制，为未来进一步用于临床打下理论基础。