Grant: Project Grant

In many diseases, post-mortem analysis of the brain reveals an abundance of swellings on axons - the wire-like structures that carry information across the brain - in the cerebellum, a brain region involved in motor coordination. This has led scientists to hypothesize that these axonal swellings contribute to the pathology that causes motor coordination deficits. Our results, however, suggest that this may not be true. The overall goal of this grant is to understand how these axonal swellings function in health and disease. We have surprising results from healthy brain tissue showing that axon swellings improve, not impair, the function of axons, and that this causes mice to learn better. Now we want to determine if axonal swellings do the same thing in disease. We hypothesize that axon swellings are something that the brain produces to repair axonal dysfunction. We will study the function of axonal swellings in two different diseases: one, a mouse model of ataxia, and the second a mouse model of Multiple Sclerosis (MS). Both display prominent axonal swellings, and in MS mice especially, axons eventually degenerate profoundly. We will test whether axonal swellings contribute to axonal dysfunction or work to counteract it. We will also unravel the mechanisms by which axonal swellings form, what role they serve in the developing brain, and where they are located and how long they persist in the intact brain. By studying the role of axonal swellings in health and disease, we hope to deeper our understanding of the brain's mechanisms of healing, which may lead to new understanding about disease mechanisms, and perhaps new treatment strategies.