St. Jude Research Study Reveals Mechanisms of Neuron Receptor Function in the Brain

St. Jude Children's Research Hospital (ALSAC)
Saturday, 1 April 2000

(Memphis, Tennessee, April 1, 2000 ) Research led by developmental neurobiologist Michisuke Yuzaki, M.D., Ph.D., at St. Jude Children's Research Hospital shows how glutamate receptors work between neurons in the brain. This understanding paves the way for more definite study in protecting neurons from glutamate receptor-related neuronal death in brain diseases.

"Neurons communicate with each other by glutamate signaling," Yuzaki said. "Glutamate is released from one neuron and is received by the next neuron that is equipped with glutamate receptors. Upon receiving glutamate, a glutamate receptor opens a 'gate' in the cell membrane, allowing ions to flow across the membrane. If glutamate receptors are under-stimulated or over-stimulated, which is observed in many brain diseases, neurons die."

The goal is to fine-tune ion flows by the opening and closing of the gate, a process called gating. "This will maintain the optimal level of stimulation in neurons."

Yuzaki's research will be published April 1 in Nature Neuroscience magazine. "Understanding the gating mechanism by which ion channels open and close has been a central goal of ion channel research since the beginning," he said. "In this paper, we demonstrated that gating is achieved by only a small region of glutamate receptors. In addition, by introducing a mutation in this region of delta2 subtype of glutamate receptors, of which function has been a mystery, we could show that delta2 receptors function as ion channels. Understanding the function of delta2 glutamate receptor is essential for understanding cerebellum function, such as coordination of muscle action."

Yuzaki's research proposes the gate structure of mutated glutamate receptors 'resides' in a small extracellular region of glutamate receptors. Having found these discoveries, Yuzaki's team can now begin exploring the possibility of modifying gate processes by applying drugs to neurons, and eventually to protect neurons from over-stimulation of glutamate receptors during disease processes.

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org