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. 

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
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As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…