15 August 2011

Intestinal protein linked to ADHD

by Kate Melville

Researchers are increasingly linking gut function to a variety of neuropsychiatric disorders. Now, a new study suggests that a biochemical pathway long associated with diarrhea may provide a new therapeutic target for treating Attention Deficit Hyperactivity Disorder (ADHD). The researchers, from China and the United States, report on their findings in Science.

The intestinal membrane receptor protein guanylyl cyclase-C (GC-C) has been studied in the past for its role in diarrheal disease and other intestinal functions. In the current study, the researchers discovered that the receptor is also expressed in critical areas of the brain.

Using a mouse model in which the GC-C receptor is knocked out, the researchers found the mice exhibit hyperactivity and attention deficits. It is the first time that GC-C has been linked to a neuropsychiatric disorder.

"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 senior author Dr. Minmin Luo, from Tsinghua University in Beijing. "Working through a protein kinase called PKG [cGMP-dependent protein kinase], 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 behavioral and physiological functions for the GC-C/PKG signaling pathway in the brain," said Dr. Luo. "The GC-C/PKG signaling pathway may lead to novel treatments for other disorders, such schizophrenia, Parkinson's disease and addiction."

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Source: Cincinnati Children's Hospital Medical Center