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2017 Grants - Igarashi
In Vivo Entorhinal-Hippocampal Synchronization in APP Knock-in Mice
Kei M. Igarashi, Ph.D.
University of California, Irvine
2017 Alzheimer’s Association Research Grant (AARG)
How might changes in the brain’s electrical rhythms between areas of the brain promote Alzheimer’s disease?
Electrical activity in the brain often exhibits certain rhythms, some of which may affect memory and other cognitive functions. Studies indicate that these rhythms become altered in Alzheimer’s disease, possibly leading to cognitive problems that characterize the disorder. As a result, several researchers are now exploring whether memory function in people with Alzheimer’s can be improved by the use of deep-brain stimulation. Deep-brain stimulation is often described as a brain “pacemaker”, using thin electrodes that are implanted directly into specific brain regions and deliver defined electrical impulses to mimic natural electrical activity. This procedure may help to restore normal brain rhythms and impact an individual’s memory. However, scientists do not yet know exactly how electrical stimulation affects brain function, especially in the hippocampus and entorhinal cortex, brain regions that are crucial for memory and are especially vulnerable in early-stage Alzheimer’s disease.
In preliminary research with rats, Kei M. Igarashi, Ph.D., and colleagues have been studying how electrical brain activity affects memory performance. They found that the rats’ memory function was strong when certain electrical rhythms between the entorhinal cortex and hippocampus were synchronized. Their result suggests that the desynchronization of electrical circuit between those key brain regions may be among the first to change in Alzheimer’s — and that restoring electrical brain stimulation may provide a way to moderate such damage and prevent or slow the progress of dementia.
The investigators will use their current grant to confirm and expand on their earlier work. For this effort, they will employ a mouse model engineered to develop variations of a gene called amyloid precursor protein (APP) that cause familial Alzheimer's disease, the rare inherited form of the disorder. Their “APP knock-in” mouse will develop beta-amyloid plaques and other brain changes that closely mimic changes seen in humans with Alzheimer’s. Dr. Igarashi’s team will measure electrical rhythms in the rodents’ hippocampus and entorhinal cortex over time, in order to determine how these rhythms are affected by Alzheimer’s progression. Next, they will administer electrical brain stimulation to their mice to determine whether this treatment may slow or reverse memory loss.
The results of this effort could improve our understanding of how electrical activity changes affect memory in Alzheimer’s disease. Ultimately, this understanding could lead to novel brain stimulation therapies for dementia.