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2017 Grants - Grunke
Plasticity of Entorhinal-Hippocampal Network in the Aged Brain
Stacy Ann Decker Grunke, Ph.D.
Baylor College of Medicine
2017 Alzheimer's Association Research Fellowship (AARF)
How does aging affect the ability of the brain to make new connections between nerve cells?
In recent years, a major focus of Alzheimer's research has been the identification of the very earliest changes that occur in the brain. Treatments that target these early brain changes could slow the progression of Alzheimer's disease. At an early stage, called mild cognitive impairment (MCI), individuals may show signs of memory loss and difficulty in thinking; in these early stages, the connections between nerve cells in two specific areas that talk to each other, the entorhinal cortex and the hippocampus, start to degrade.
Research Plan Stacy Ann Decker Grunke, Ph.D., and colleagues developed a new, genetically engineered mouse to study the nerve cells specifically in the entorhinal cortex. In these mice, treatment with a chemical "turns off" the entorhinal nerve cells, preventing them from conducting electrical signals to other nerve cells in the brain. They found that when entorhinal nerve cells are turned off, they degrade and eventually die, similar to what happens in MCI. They also found that despite the loss of a large number of entorhinal nerve cells, young mice are able to rebuild connections between the remaining nerve cells, but aged mice are not. The ability of the brain to redirect connections between nerve cells is called "plasticity."
Dr. Grunke and colleagues propose to use their new mouse model to compare the plasticity of the entorhinal cortex nerve cells in young and aged mice. First, they will determine how the young mouse brain is able to recover after loss of entorhinal nerve cells. They will measure the electrical activity and growth patterns of nerve cells as they degrade and die, and observe how surviving nerve cells change their activity and growth to rebuild connections that were lost. Then they will examine aged mice to determine how the loss and recovery of entorhinal nerve cells is different from that seen in the young mice. Finally, they will investigate how the inability of entorhinal nerve cells to recover connections in the brain (low plasticity) in the aged mice leads to poor learning and memory.
This study may help determine how the ability of nerve cells in the brain fail to make new connections (plasticity) with age, making the aging brain more vulnerable to development of MCI and Alzheimer's disease. The research may also lead to the identification of new therapies that can preserve connections or possibly stimulate new connections between nerve cells in the entorhinal cortex and slow the progression of Alzheimer's disease.