CAREER: Magnetic Stimulation and Myelination

脱髓鞘是神经纤维保护层（髓鞘）的退化，是与神经系统疾病（如多发性硬化症、阿尔茨海默病和帕金森病）相关的常见副作用。目前治疗脱髓鞘轴突的方法需要重新浸泡和支持少突胶质细胞，这是一种促进髓鞘发育的特殊细胞。科学界已经发现，当施加电、光、磁等外部刺激时，神经元会被激活。其中，磁刺激是唯一一种非侵入性的再生体内受损神经元的方法。该项目旨在发现磁刺激对髓鞘形成过程的影响的一种新的、基本的理解，这可能最终导致为下一代神经医学设备的开发创造新技术和工具。随后，这些设备可能会在未来医学界产生神经系统疾病的创新治疗方法。此外，该项目将吸引K-12，本科生和研究生，激励他们从事再生神经工程的职业。特别是，该项目将采用外展活动和实践活动，积极招募女性，第一代，代表性不足的和退伍军人的学生加入该项目，并准备他们为这个令人兴奋的领域做出贡献。PI的总体职业目标是在北卡罗来纳大学夏洛特分校机械工程系生物医学工程与科学中心建立一个非常成功的神经工程研究和培训项目。为此，本项目的目标是研究磁刺激（MSTIM）诱导少突胶质细胞（OLs）轴突的髓鞘形成以及MSTIM在髓鞘形成中的信号机制。神经系统有髓轴突脱髓鞘是神经系统疾病和脊髓损伤的一个有害特征。然而，当内源性少突胶质细胞祖细胞（OPCs）分化为新的髓鞘性少突胶质细胞（OLs）时，受损的轴突可以被修复（即再髓鞘化）。然而，由于OPCs无法分化OLs，因此内源性OLs对轴突的再髓鞘形成是有限的。神经元的电活动在OPC分化和轴突髓鞘形成中起着必要的作用。神经调节是一种新兴的神经技术，通过刺激或抑制功能失调的神经回路使其进入更生理的状态，是诱导髓鞘形成的有效工具。体外电刺激（ESTIM）和光遗传刺激（OSTIM）神经元可以增加神经活动并增强轴突的髓鞘形成，但这是一种侵入性方法。一种类似的技术，磁刺激（MSTIM），是一种非侵入性的神经调节形式，也可以调节神经活动。本研究计划有三个目标：(1)建立MSTIM诱导神经活动依赖的髓鞘形成的体外模型；(2)研究MSTIM诱导轴突的OPCs分化和髓鞘形成；(3)研究MSTIM诱导髓鞘形成的神经元和OPCs释放的神经营养因子和信号分子。结果有望使人们了解MSTIM与神经系统之间相互作用的基本机制。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Demyelination is the degradation of the protective covering (myelin sheath) of nerve fibers, a common side effect associated with neurological disorders, e.g., multiple sclerosis, Alzheimer’s disease and Parkinson’ disease. Current methods to treat demyelinated axons require re-immersion and support of oligodendrocytes, special cells that promote myelin development. The scientific community has found that neurons can be activated when an external stimulation is applied such as Electrical, Optogenetic and Magnetic stimulation. Of these, Magnetic stimulation is the only non-invasive method for regenerating injured neurons in the body. This project seeks to discover a new, fundamental understanding of the effects of Magnetic stimulation on the myelination process that may eventually lead to the creation of new techniques and tools for the development of the next generation of neurological medical devices. Subsequently, these devices may spawn innovative treatments of neurological diseases by the medical community in the future. Additionally, this project will engage K-12, undergraduate, and graduate students to inspire them to pursue careers in Regenerative Neural Engineering. In particular, this project will employ outreach activities and hands-on activities to actively recruit female, first generation, underrepresented, and veterans’ students into the project and prepare them to contribute to this exciting field. The PI’s overarching career goal is to establish a highly successful neural engineering research and training program within the Center for Biomedical Engineering and Science in the Department of Mechanical Engineering at the University of North Carolina, Charlotte. Towards this goal, the goal of this project is to investigate magnetic stimulation (MSTIM) induced myelination of axons by oligodendrocytes (OLs) and the signaling mechanisms of MSTIM in myelination. Demyelination of myelinated axons in the nervous system is a deleterious feature of neurological diseases and spinal cord injuries. However, damaged axons can be repaired (i.e., remyelinated) when endogenous oligodendrocyte progenitor cells (OPCs) differentiate into new myelinating oligodendrocytes (OLs). Remyelination of axons by endogenous OLs, however, is limited due to OPCs’ failure to differentiate OLs. Electrical activity of neurons plays a necessary role in OPC differentiation and myelination of axons by OLs. Neuromodulation, an emerging neurotechnology, excites or inhibits dysfunctional neuronal circuits to alter them into a more physiological state and can be an effective tool for inducing myelination. In vitro electrical stimulation (ESTIM) and optogenetic stimulation (OSTIM) of neurons have been found to increase neural activity and enhance myelination of axons, but are invasive methods. A similar technique, magnetic stimulation (MSTIM), is a non-invasive form of neuromodulation that also modulates neural activity. The Research plan is organized under three objectives: (1) establish an in vitro model of neural activity-dependent myelination by MSTIM, (2) investigate MSTIM induced differentiation of OPCs and myelination of axons, and (3) investigate the neurotrophic factors, and signaling molecules released from neurons and OPCs with MSTIM-induced myelination. Outcomes are expected to enable an understanding of the fundamental mechanisms of interactions between MSTIM and the nervous system.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.