Boosting Myelination Using Visual Flicker in the Acute Cuprizone Intoxication Model
Abstract
Myelin is an insulating substance that wraps around healthy axons -- the wires that connect neurons -- and allows them to communicate rapidly, reliably, and over long distances. Demyelinating diseases such as multiple sclerosis (MS) damage myelin and result in visual, motor, and cognitive deficits. Because the search for drugs that restore myelin has been unsuccessful, more than one million people in the United States alone suffer from the progressively worsening symptoms of MS. About 8 years ago, researchers discovered that increasing neural activity (in mice) boosts myelin growth. So far, no one has tested whether this also works in humans, presumably because the tools used to increase neuronal activity in mice are not suitable for use in humans. Recently, however, we found that a particular kind of flickering light (Flicker for short) results in a widespread increase in neuronal activity throughout the brain. This finding led us to the new idea underlying this proposal: could increasing neural activity using Flicker stimulate the regrowth of myelin? This project takes the first step from this idea toward a novel, non-pharmaceutical treatment for MS. Specifically, we want to show that Flicker boosts myelination in mice. Following a common approach in the field, we will feed mice a diet with the toxin cuprizone mixed in; over a few weeks, this results in almost complete demyelination and strong impairments in visual and motor behavior. After returning the animals to a regular diet, they recover, at least partially. We will measure their impairments using sensitive, noninvasive measures of myelination (visual evoked potentials, optomotor responses, and wheel running). Animals will receive either a daily dose of Flicker or no treatment. We predict that mice exposed to Flicker will show fewer impairments and a faster or more complete recovery. We aim to use the brain s innate potential for (re)-myelination. Therefore, this project falls within the MSRP Focus Area that seeks to understand and use the Central Nervous System s Regenerative Potential in Demyelinating Conditions. Our immediate goal (less than 2 years) is to provide evidence that Flicker boosts myelination in mice, but our long-term goal (2-5 years) is to develop this into a novel treatment approach in humans. We designed the animal experiments with this in mind; the Flicker treatment and our experimental measures of impairments all have analogous methods appropriate for use in humans. This project s outcomes will therefore help design a randomized clinical trial to test our idea in MS. If we are successful, this could lead to a novel, non-pharmaceutical approach to remyelination that may stop or even revert the progression of MS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310568
Entities
People
- Bart Krekelberg
Organizations
- Rutgers University
- United States Army