Ziburkus Receives Two-Year Grant from Alzheimer’s Association
New Investigator Research Grant Funds Studies of Inhibitory Neurons in the Hippocampus

Jokubas Ziburkus, assistant professor of biology and biochemistry at the University of Houston, received a New Investigator Research Grant from the Alzheimer’s Association. The two-year, $100,000 grant funds his project entitled, “Inhibitory Neuron and Circuit Dysfunctions in Alzheimer’s Disease Model.”

The project will examine one of the fundamental processes of brain dysfunction in a common form of dementia – Alzheimer’s disease, and the results may suggest strategies to prevent or restore dysfunction.

Using mice that have been genetically engineered to have Alzheimer's-like disease in the brain, the study will look at inhibitory nerve cells (neurons) in the hippocampus, one of the first regions of the brain affected by Alzheimer's disease. The hippocampus 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 causes dysfunction of neurons in the hippocampus are not well understood.

The project is an excellent example of the many collaborative efforts between UH scientists and Texas Medical Center researchers. Ziburkus’ project combines the research efforts of the biology and biochemistry department with those of Jason Eriksen, UH assistant professor of pharmacology and pharmaceutical sciences, and Matthew Rasband, a professor of neuroscience at Baylor College of Medicine.

In previous studies, Ziburkus and colleagues performed electrical recordings of neuronal 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 excitatory cells in the dentate gyrus, granule cells, had unusually strong responses to signals from other neurons. The researchers believe this is caused by dysfunction in the inhibitory neurons that normally inhibit granule cell activity. This abnormal activity is reminiscent of activity that is seen in epileptic brains.

For this grant, the research involves an extensive series of studies of the hippocampus’ inhibitory neurons. Using the Alzheimer’s-like mice, the researchers will perform electrical recordings and optical imaging studies at different ages to study the activity of inhibitory neurons and hippocampal circuits. They will also use imaging methods to measure the accumulation of beta-amyloid in the hippocampus to determine if beta-amyloid levels are related to neuron dysfunction.