Mice with 'mohawk hairstyles' reveals clues to development of autism
Mice with "mohawks" hairstyles have helped scientists link autism to 2 biological pathways in brain.
Findings should help narrow the search for genetic contributions of autism and suggest new routes for therapy
But both events happened in a lab at NYU Langone Medical Center, months after an international team of neuroscientists bred hundreds of mice with a suspect genetic mutation tied to autism spectrum disorders.
Almost all the grown mice, the NYU Langone team observed, had sideways, "overgroomed" hair with a highly stylized center hairline between their ears and hardly a tuft elsewhere. Mice typically groom each other's hair.
Now and for what NYU Langone researchers believe to be the first time, an autistic motor behavior has been traced to specific biological pathways that are genetically determined.
The findings, says senior study investigator Gordon Fishell, PhD, the Julius Raynes Professor of Neuroscience and Physiology at NYU Langone, could with additional testing in humans lead to new treatments for some autism, assuming the pathways' effects as seen in mice are reversible.
In the study, researchers knocked out production in mice of a protein called Cntnap4. This protein had been found in earlier studies in specialized brain cells, known as interneurons, in people with a history of autism.
Researchers found that knocking out Cntnap4 affected two highly specialized chemical messengers in the brain, GABA and dopamine. Both are so-called neurotransmitters, chemical signals released from one nerve cell to the next to stimulate similar sensations throughout the body. GABA, short for gamma-aminobutyric acid, is the main inhibitory neurotransmitter in the brain. It not only helps control brain impulses, but also helps regulate muscle tone. Dopamine is a well-known hormonal stimulant, highly touted for producing soothing, pleasing sensations.
Among the researchers' key findings was that in Mohawk-coiffed mice, reduced Cntnap4 production led to depressed GABA signaling and overstimulation with dopamine. Researchers say the lost protein had opposite effects on the neurotransmitters because GABA is fast acting and quickly released, so interfering with its action decreases signaling, while dopamine's signaling is longer-acting, so impairing its action increases its release.
The study has been published online in the journal Nature.
(Posted on 26-05-2014)