A new international study suggests a protein receptor found in the gastrointestinal tract is also found in important areas of the brain.
When the receptor was removed in mouse models, the mice became hyperactive and displayed problems with their ability to pay attention. This could help with scientists’ understanding of attention deficit hyperactivity disorder (ADHD).
According to scientists, the intestinal membrane receptor protein, guanylyl cyclase-C (GC-C) has been studied for over two decades for its role in diarrheal disease and other intestinal functions. In fact, it had been thought that GC-C was found primarily in the intestine.
In the current study, scientists in China led by Dr. Minmin Luo, a neurobiologist at the National Institute of Biological Sciences, Beijing, collaborated with pediatrician Dr. Mitchell Cohen of the Cincinnati Children’s Hospital Medical Center. They found that the receptor is also expressed in critical areas of the brain.
Using a mouse model, scientists genetically removed the GC-C receptor and found the mice exhibited hyperactivity and attention deficits. It is the first time that GC-C has been linked to neuropsychiatric disorder, according to the researchers.
Researchers learned that neurons selectively express GC-C which increases brain dopamine levels thereby regulating mouse attention and activity level.
When the researchers treated the GC-C knockout mice with amphetamine-based ADHD medication, 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 Luo.
“The data also suggest new therapeutic targets for neuropsychiatric disorders related to malfunctions of midbrain dopamine receptors.”
Results from the current study are published in Science.
One of the most prevalent human behavioral disorders, ADHD has been linked to imbalances in the dopamine system. The researchers noted in the study that its findings – mice exhibiting reduced dopamine levels and related behavioral problems – are consistent with the biochemical characteristics of human ADHD.
“This could make the GC-C knockout mouse a good research model for ADHD and other behavioral disorders,” said Cohen. “Efforts to develop activators or inhibitors of the GC-C/PKG signaling pathway may lead to novel treatments for other disorders, such schizophrenia, Parkinson’s disease and addiction.”