CINCINNATI A biochemical pathway long associated with diarrhea and intestinal function may provide a new therapeutic target for treating ADHD (Attention Deficit Hyperactivity Disorder) other neuropsychiatric disorders, according to a team of scientists from China and the United States reporting Aug. 11 in Science.
Scientists have for the last quarter century studied the intestinal membrane receptor protein, guanylyl cyclase-C (GC-C) for its role in diarrheal disease and other intestinal functions, according to Mitchell Cohen, M.D., U.S. author on the study and director of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's Hospital Medical Center. In fact, it had been thought that GC-C was found primarily in the intestine.
In the current study, scientists in China who collaborated with Dr. Cohen discovered that the receptor is also expressed in critical areas of the brain. The senior author on the study is Dr. Minmin Luo, a researcher at the National Institute of Biological Sciences and Tsinghua University in Beijing.
Using a mouse model developed in Dr. Ralph Giannella's laboratory at the University of Cincinnati, in which the GC-C receptor is deleted, or knocked out, the researchers found the mice exhibit hyperactivity and attention deficits. It is the first time that GC-C has been linked to neuropsychiatric disorder, according to the researchers.
"We show that the neurons selectively express GC-C and that its activation amplifies the excitatory responses mediated by other receptors on dopamine neurons in the midbrain," said Dr. Luo. "Working through a protein kinase called PKG, GC-C activity increases brain dopamine levels and thus regulate mouse attention and activity level."
When the researchers treated the GC-C knockout mice with amphetamine-based ADHD medication and a PKG activator, it reversed their hyperactive, inattentive behavior.
"The results indicate important behavio
|Contact: Nick Miller|
Cincinnati Children's Hospital Medical Center