AsianScientist (Aug. 16, 2011) – Chinese scientists, working with collaborators in the United States, have discovered that attention deficit hyperactivity disorder (ADHD) and other neuropsychiatric disorders may be caused by the abnormal function of a protein better known for its role in diarrhea and intestinal disease.
The intestinal membrane receptor protein guanylyl cyclase-C (GC-C), which was previously thought to be found primarily in the intestine, is a key receptor for diarrhea-causing enterotoxins produced by pathogens such as Escherichia coli (E. coli).
However, scientists led by Dr. Minmin Luo at the National Institute of Biological Sciences and Tsinghua University in Beijing have discovered that GC-C can also be found in critical areas of the brain.
To find out what function the GC-C receptor performs in the brain, the scientists developed a mouse model in which the gene encoding the GC-C receptor is knocked out, or deleted from its genome. They found that mice which lacked this receptor exhibit hyperactivity and attention deficits.
The mice also had reduced levels of dopamine, which is consistent with the biochemical characteristics of human ADHD. The study, published online in Science on 11 August, is the first time 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,” says Dr. Luo. “Working through a protein kinase called PKG, GC-C activity increases brain dopamine levels and thus regulates mouse attention and activity level.”
When the researchers treated the GC-C knock-out mice with amphetamine-based ADHD medication and a PKG activator, it reversed their hyperactive, inattentive behavior.
The data also suggests that activators or inhibitors of GC-C/PKG signaling may be useful in treating a variety of neurobehavioral disorders related to abnormal dopamine levels, such as schizophrenia, Parkinson’s disease, and addiction.
The researchers hope that the GC-C knock-out mouse model would be a useful tool for neurobehavioral disorder research and could help in the development of novel treatments for ADHD and other such disorders.
The article can be found at: Gong R et al. (2011) Role For The Membrane Receptor Guanylyl Cyclase-C In Attention Deficiency And Hyperactive Behavior.
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Source: University of Cincinnati.
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