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

José Manuel Baizabal Carballo, Ph.D., Indiana University Bloomington
Heterochromatin Mechanisms of Cortical Expansion
Neurodevelopmental disorders, such as autism and schizophrenia, are frequently associated with mutations in genes that encode chromatin-modifying enzymes. A subset of these mutations is thought to disrupt compacted chromatin (heterochromatin),…
Jessica L. Bolton, Ph.D., Georgia State University
Chemogenetic Tools in Microglia as a Novel Therapeutic Approach for Brain Disorders
All humans are born with a unique combination of genes, which contribute greatly to who we are. However, early-life experiences such as trauma or hardship, particularly during the first few…
Junyue Cao, Ph.D., The Rockefeller University
Elucidate the Molecular and Cellular Targets of Caloric Restriction in Rejuvenating Aged Mammalian Brain
As we age, the brain’s ability to function declines, increasing the risk of cognitive impairments and neurological diseases like Alzheimer’s and Parkinson’s. Our research investigates how caloric restriction (CR), a…
Vasileios Christopoulos, Ph.D., University of Southern California
Understanding the Mechanisms of Micturition in the Brain and Spinal Cord
This research aims to better understand how the brain and spinal cord work together to control urination, a process known as micturition. In healthy individuals, this process is carefully coordinated…