CAREER: Magnetic Stimulation and Myelination

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.