Autism is a neurobiological disorder that can present in hundreds of different ways. Medical experts refer to the "autism spectrum" because there are so many variations in how it impacts individual patients. While there is no cure for autism and treatments are limited to behavioral therapy that isn't always effective, the race to find out more about the disorder is on.
Most researchers agree that there is a genetic link to autism. Research that focused on genetics has found several mutations in genes that are linked to autism spectrum disorders. Recent findings by a team at Washington University School of Medicine in St. Louis suggest that patients with autism could have too many synaptic connections happening in cerebellum and this overload could be part of what causes autism. Research in 2014 at Columbia University showed that the brains of children with autism had more synaptic connections, but did not identify a genetic link that could be causing them.
Azad Bonni, MD, Ph.D. is the senior author of the study and the head of the Department of Neuroscience at the WU School of Medicine. He explained, "This study raises the possibility that there may be too many synapses in the brains of patients with autism. You might think that having more synapses would make the brain work better, but that doesn't seem to be the case. An increased number of synapses creates miscommunication among neurons in the developing brain that correlates with impairments in learning, although we don't know how."
One of the critical genes in autism are the ubiquitin ligases. These genes are like a dispatcher, communicating tasks to neurons in the brain. The genes attach a molecular tag to ubiquitin proteins to signal the neurons and tell them how to react. Patients who have an autism spectrum disorder could have a mutation in one of these key genes. That mutation disrupts the normal function of the gene but connecting that disruption to the brain and subsequently to autism behaviors hasn't been well defined.
To find out more on how these genes were related to autism, they used a mouse model that had been genetically altered. The ubiquitin gene RNF8 was removed from the cerebellum of mouse pups. In the mice that didn't have the RNF8 protein, the team noted that there were about 50% more electrical connections than in the mice who had not been altered. The electrical signal from these synapses was also double the strength of that in the normal mice.
One of the functions of the cerebellum is to regulate movement. Some patients who have autism have stiff or uncoordinated movements. While the altered mice appeared to have standard motor control, when the scientists attempted to teach them new motor skills, they were not able to perform very well. In one task, researchers would blink a light in the cage and follow that with a puff of air to the eyes of the mice. In about a week, close to 75% of the genetically normal mice learned to shut their eyes when the light blinked on and off. The mice that had been altered only did this about 30% of the time. The cerebellum is also involved in learning and attention, and these are problem areas in autism as well.
After publishing their results, Bonni and his colleagues at WU inhibited all of the other ubiquitin genes that are related to autism, and the results were the same. In each case, the number of synaptic connections was double that of the mice whose genes were not modified. They hope to continue the work to see if the genetic mutation that causes an overload of electrical impulses in the brain can be translated to research with humans. Finding a way to correct these gene mutations could be a significant step in finding a way to treat autism. Take a look at the video to learn more about what neuroscientists know about the causes of autism and the genetic factors that surround the disorder.