LEXINGTON, Ky. (June 4, 2021) – University of Kentucky Department of Neuroscience Professor Greg Gerhardt, Ph.D. hypothesizes that the balance of glutamate and gamma-aminobutyric acid (GABA) – two major neurotransmitters in the brain – contributes to Alzheimer’s disease -Disease and age-related decline in cognition and memory.
Now the UK College of Medicine researcher and his team want to find out. Gerhardt has developed a new technology that can measure the two neurotransmitters at the same time every second. This is the first time this has happened in vivo – or in the living brain of awake animals.
Thanks to a five-year grant of US $ 2 million from the National Institute on Aging, Gerhardt is starting a study to research the balance of GABA and glutamate in the aging brain. The program will provide answers to longstanding questions that could help develop new treatments for Alzheimer’s disease.
Gerhardt says it is a high point in his almost 40 years of brain research.
“This grant is based on brain recording technologies that my lab has worked on for decades. We now have the ability to measure these two molecules in vivo, which was very difficult in the past, ”said Gerhardt, who heads the UK Center for Microelectrode Technology. “We’re excited to answer some questions that the world is very interested in.”
Gerhardt, who has been working in Great Britain since 1999, studies the course and treatment of neurodegenerative diseases, in particular Parkinson’s and Alzheimer’s. To do this, he developed complex medical devices to measure signal molecules in the brain. His research has helped scientists understand the difference between normal changes that occur in the brain with aging and the progression of such diseases. Understanding could lead to treatments to stop the disease from progressing.
GABA, the brain’s main inhibitory neurotransmitter, lowers the activity of nerve cells in the brain and central nervous system. Glutamate, the main excitatory neurotransmitter, increases their activity. Both play a crucial role in memory development.
Gerhardt says that GABA and glutamate counteract each other and that balance is important for normal brain function and memory. Little is known, however, about how this balance works, especially in the aging brain. In addition, previous studies showing irregular changes in the balance of glutamate and GABA in individual aging brain structures are ambiguous and often contradictory.
To oversee the study, Gerhardt is working with British colleague Paul Murphy, Ph.D., Associate Professor in the Department of Molecular & Cellular Biochemistry, one of the world’s leading experts on Alzheimer’s animal models.
The team will use Gerhardt’s enzyme-based brain recording technology to measure GABA and glutamate function in the brain of both normally aging mice and those with Alzheimer’s-like pathology and memory disorders. The device consists of a metallized microelectrode array (MEA) with enzymes that measure the two neurotransmitters directly in vivo.
The mice are then tested for changes in spatial memory – the ability to remember different objects and their locations, and novel memory – the ability to identify new objects in an environment. Then their test results are compared to measurements of glutamate and GABA levels to determine possible correlations between neurotransmitter levels, behavior, and brain pathology.
Gerhardt and his team hope that the study results will help in the future development of treatments for Alzheimer’s. There is currently no cure for the disease or any way to stop or slow its progression. The only treatment options available are for symptom relief.
“Although there are currently FDA-approved drugs that change the way GABA and glutamate work, there is nothing to improve their balance,” said Gerhardt. “What if it could be safely adapted that actually improved patients’ memory and slowed the progression of the disease, rather than just relieving symptoms? This study could be an important step in the development of such a treatment. “
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under grant number RF1AG070952. The authors are solely responsible for their content and do not necessarily represent the official views of the National Institutes of Health.