Repetitive behaviors, like those seen in obsessive-compulsive disorder (OCD), may be controlled and suppressed by a network of proteins in the brain, according to new research published in Nature Neuroscience.

The research centers on the role of two very similar proteins, known as Hdac1 and Hdac2, in the brain. These proteins are molecular machines that help regulate the activity of genes throughout the body. Still, how they affect neuronal function in the brain has remained largely unknown.

Now, in work published September 26, 2016, a team of scientists from the University of Texas Southwestern defined the role of these proteins, uncovering a network that controls repetitive behaviors in mice. The team was led by Lisa M. Monteggia, Ph.D., a 2001 and 2003 NARSAD Young Investigator grantee, 2010 NARSAD Independent Investigator grantee, 2014 NARSAD Distinguished Investigator grantee, and 2005 Freedman Prizewinner.  The team simultaneously deleted both the Hdac1 and Hdac2 genes in the forebrain of mature mice. That’s the part of the brain responsible for higher-level cognitive functions like learning and memory. Loss of the two proteins that these genes encode had dramatic effects. The affected animals had smaller brains and were less active than normal. They also died prematurely.

The researchers also noted that the animals exhibited pronounced lesions on their skin. Watching the animals for extended periods, the scientists discovered that the animals were grooming excessively – to the point that they rubbed their own skin raw.

The team tried to define the molecular pathway that controls this behavior. They found that Hdac1 and Hdac2 work together with a protein known as MeCP2. Mutations in MeCP2 are known to cause Rett syndrome and are observed in some patients with autism. The team found that the three proteins together regulate another molecule, called Sapap3, that is involved in grooming behavior.

This network of related proteins functions specifically in the striatum, an area of the brain that controls voluntary movements, especially for rewards. Together, the research demonstrates that the proteins form a pathway that suppresses excessive grooming in mice, offering molecular insights into the mechanisms that may control repetitive behaviors in humans as well.

The research team also included Megumi Adachi, Ph.D., a 2008 NARSAD Young Investigator grantee, and Ege Taner Kavalali, Ph.D., a 2012 NARSAD Distinguished Investigator.