Mechanisms of Myelin Degeneration and Clearance in the Live Brain

2019 Seed Grant
Robert A. Hill, Ph.D.
Dartmouth College

Carl & Marilynn Thoma Foundation Seed Grant

A complex cell structure called myelin has evolved to speed up and finely tune the transmission of electrical signals in the brain. In numerous human diseases, myelin is damaged and must be removed before tissue repair can occur. We know very little about the cellular dynamics and mechanisms involved in this process. We have developed advanced techniques for high resolution subcellular optical imaging of these events in the live animal over a wide range of temporal scales from seconds to months. By applying these tools this project will investigate how damaged myelin is dynamically cleared by resident glial cells and the consequences of defective clearance on axonal maintenance and myelin repair. These studies will provide fundamental biological insight into this important process and likely reveal potential therapeutic windows for manipulating these processes. Importantly these studies have direct clinical relevance as defective myelin clearance is implicated in delayed or incomplete myelin repair seen in aging, advanced stages of multiple sclerosis and in other neurodegenerative diseases. 

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Sarah C. Goetz, Ph.D., Duke University
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Byoung Il Bae, Ph.D., University of Connecticut
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