How can damage to nerve cells that regulate activity throughout the brain cell network promote risk of dementia?
Christopher Gabel, Ph.D.
Boston, MA - United States
Specific types of nerve cells in the brain send signals that can increase or decrease the activity of the brain cell network. These cells are known, respectively, as excitatory and inhibitory nerve cells. Studies have revealed a loss of balance in these signals in genetically engineered Alzheimer’s-like mice that makes the brain cells overly active. Other studies have shown that restoring the balance of excitatory and inhibitory nerve cell activity reduces the clumping of beta-amyloid in the brain (a hallmark characteristic of Alzheimer’s) and has been shown to improve cognition. Scientists, however, remain unclear exactly how nerve cell activity imbalance affects brain health and function.
Dr. Christopher Gabel and colleagues will work to clarify the biological mechanisms that link excitatory and inhibitory nerve cell activity with dementia risk. The study will utilize an animal model called Caenorhabditis elegans, a species of roundworm that develops similar dementia-related brain cell damage and cognitive decline as humans. For this study, the researchers will use an advanced brain scan technique that uses a fluorescent dye (chemical compound) that can “highlight” nerve cells of interest throughout the brain of the worms. Dr. Gabel and colleagues will compare nerve cell activity in normal and dementia-like roundworm brains. They will then assess how changes in specific inhibitory and excitatory nerve cells are linked to changes in activity – including the way nerve cells across the brain communicate with each other. They will also look for individual genes that may play a role in these links. Finally, the investigators will examine whether a specific protein, which has been shown to preserve normal activity in individual nerve cells, can prevent or reduce the activity imbalance and dementia-related damage throughout the roundworm brain.
The results of this project could shed new light on how changes in nerve activity promote one’s risk for Alzheimer’s. They could also help identify genetic and protein targets that may be used in the development of future dementia therapies.
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