Many people who have been diagnosed with autism perform repetitive motions in order to soothe themselves and reduce stress when they become overwhelmed. These motions can include rocking back and forth, wringing hands, shaking their head, or flapping their arms, among many others. Researchers at NYU Langone Center recently realized that mice with autism-like symptoms also exhibit repetitive behavior, sometimes in the form of grooming. This allowed them to link two biological pathways with autism. The research was led by Gordon Fishell and the paper was published in Nature.
The study was originally exploring a particular genetic mutation which the researchers believed to be a precursor to Autism Spectrum Disorder. They bred hundreds of mice with this mutation for study. Months later when the mice had fully grown, they began to groom themselves excessively. This was very similar to the repetitive movements performed by those with autism. As a result, the patch of hair between their ears was spiked straight up, just like a mohawk. This was especially out of the ordinary, as mice tend to groom one another, not themselves.
These mice had been genetically altered to turn down the production of the protein Cntnap4, which plays a role in many aspects of the growth and development of neurons. Previously, the protein has been found in the interneurons (cells that connect and facilitate signals between sensory and motor neurons). When Cntnap4 was inhibited, it also affected dopamine and gamma-aminobutyric acid (GABA), which inhibits neurotransmitters and plays a role in muscle tone.
GABA and dopamine work differently, and their longevity has made for some peculiar results in the absence of Cntnap4. GABA is released and used quickly, so when it is inhibited, production production slows. This allows the brain to become overstimulated, as it cannot effective manage the signaling. Dopamine is much longer-lived, meaning that it will increase production when it becomes inhibited, increasing the happy feelings that become associated with repetitive behaviors.
"Our study tells us that to design better tools for treating a disease like autism, you have to get to the underlying genetic roots of its dysfunctional behaviors, whether it is overgrooming in mice or repetitive motor behaviors in humans," Fishell said in a press release. "There have been many candidate genes implicated in contributing to autism, but animal and human studies to identify their action have so far not led to any therapies. Our research suggests that reversing the disease's effects in signaling pathways like GABA and dopamine are potential treatment options.”
During the study, the researchers also noted that GABA and dopamine signaling do not remain constant throughout the mouse’s life. Understanding how these signaling pathways influence behavior could eventually lead to a targeted treatment for symptoms of autism.