MERIT recognizes Ticku’s research
Maharaj K. Ticku, professor of pharmacology and psychiatry at the Health Science Center, has received one of the most prestigious awards presented by the National Institutes of Health (NIH). The MERIT Award ensures the continuation of his important research through at least 2010.
The MERIT Award Program, short for "Method to Extend Research in Time," recognizes researchers with distinguished track records of scientific achievement. Dr. Ticku, who studies the genes that are affected by chronic alcohol intake, has a new five-year, $1.495 million grant from the NIH’s National Institute of Alcoholic Abuse and Alcoholism (NIAAA), and will receive a five-year grant renewal in 2005.
Dr. Ticku, a Ph.D. graduate in biochemical pharmacology from the State University of New York at Buffalo, has held NIH/NIAAA funding since joining the Health Science Center faculty in 1978.
"We are identifying elements that regulate how the body responds in alcohol dependence and withdrawal," he said. "Our goal is to understand the neurobiology of alcohol addiction. Symptoms include short- and long-term memory loss and the death of neurons, or brain cells."
His research group was one of the first to suggest that alcohol consumption may affect proteins involved in brain chemistry. Dr. Ticku has studied a pair of neurochemical messengers, GABA and NMDA, and the "receptors," or portals, through which they affect millions of brain cells. Alcohol affects both the GABA and NMDA receptors, which is important because GABA inhibits cell firing in the brain, while NMDA increases it.
"We have developed an in vitro model of chronic, repeated withdrawal from alcohol, using brain cells in culture," he said. "In these neurons we observe a ‘kindling-like’ phenomenon that results in abnormal brain cell firing; this same process may cause the delusions and deliriums seen in human alcohol withdrawal. No one knows the molecular basis of this response, but NMDA and GABA are major candidates for study."
The NMDA protein receptor is involved in learning and memory, activities that are impaired by alcohol. If NMDA is too active, cell death results. GABA is involved in motor control, and a decrease of its effect can result in anxiety or seizures.
"Drugs alter the balance," said Dr. Ticku. "Anti-anxiety agents, such as Valium, increase the GABA activity. Nearly all anesthetics increase it. In our test animals, after chronic treatment with alcohol, we see diminished GABA activity and increased NMDA activity."
The MERIT winner’s research may make it possible to develop drugs that target the underlying effects of alcohol. Sixteen different genes have been identified as playing key roles in GABA receptors’ activity, while four genes have been identified with the NMDA receptors. Scientists also have identified various subtypes of GABA and NMDA brain receptors.
"Valium causes side effects, such as drowsiness, because it works on all the GABA receptor subunits at once," Dr. Ticku says. "Better drug design will result in drugs that work on one subtype and not the others."
The research being conducted by Dr. Ticku and his colleagues contributes to our understanding about alcohol’s effects and will help in the development of therapies to benefit those at risk for alcoholism.