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2012 Grants - Ziburkus
Inhibitory Neuron and Circuit Dysfunctions in Alzheimer's Disease Model
Jokubas Ziburkus, Ph.D.
University of Houston
2012 New Investigator Research Grant
One of the first regions of the brain affected by Alzheimer's disease is the hippocampus, which is important for memory function. Beta-amyloid, a protein fragment implicated in the cause of Alzheimer's disease, also accumulates in the hippocampus during early stages of the disease, and is believed to cause dysfunction in this region. The mechanisms by which beta-amyloid cause dysfunction of nerve cells (neurons) in the hippocampus are not well understood.
Jokubas Ziburkus, Ph.D., and colleagues have performed electrical recordings of nerve cell activity in Alzheimer's-like mice, focusing on a region of the hippocampus known as the dentate gyrus. They found that the main type of cell in the dentate gyrus, granule cells, had unusually strong responses to signals from other neurons. The researchers believe this is caused by dysfunction of a third type of cell inhibitory neurons that normally inhibits granule cells activity.
Dr. Ziburkas and colleagues have proposed a more extensive series of studies of the inhibitory neurons in the hippocampus. Using mice that have been genetically engineered to have Alzheimer's-like disease in the brain, the researchers will perform electrical recording at different ages to study the activity of inhibitory neurons. They will also use imaging methods to measure the accumulation of beta-amyloid in the hippocampus in order to determine if beta-amyloid levels are related to neuron dysfunction.
Dr. Zibukus and colleagues will also use electrical recording techniques to characterize proteins that form pores in cells, ion channels, responsible for defective activity of inhibitory neurons. These studies will examine one of the fundamental processes of brain dysfunction in Alzheimer's disease, and they may suggest strategies to prevent or restore dysfunction.