Grant: Project Grant

Multiple sclerosis, stroke and spinal cord injury are common and devastating human disorders. The central nervous system is composed of two different types of tissue: gray matter, which comprises the nerve cell bodies, and white matter, which represents the nerve fibers connecting nerve cells to each other. Nerve fibers in the brains of mammals are highly specialized, being very thin (to pack millions of fibers into a small volume) and wrapped by an insulating fatty material called myelin to prevent short circuits. How this all-important myelin is damaged in human neurological disorders, and how the nerve fiber tells the myelin to start wrapping and insulating it, remain mysteries. This ongoing project has focused on chemical communication between axons (nerve fibers) and their myelin sheaths. We discovered that axons signal their myelin sheaths using chemical transmitters in a way that is very similar to how nerve cells communicate: through a chemical "synapse". This new axon-myelin synapse causes damage to myelin when excessively activated, and may be the first step in myelin loss in MS for instance. This project will explore the purpose of this axon-myelin synapse: why do axons need to talk to their myelin sheaths? What might myelin do for its axon when it senses a lot of electrical traffic traveling down the axon? We propose that myelin supports its axon by physically transferring material essential for the axon's long term survival. A breakdown of this communication and transfer may underlie diverse diseases such as MS, cerebral palsy and even psychiatric disorders such as schizophrenia and autism.