CHICAGO, Nov. 17 (Xinhua) -- Mutation in a gene linked to autism in people causes neurons to form too many connections in rodents, and that malfunctions in communication between brain cells could be the root of autism, according to a study of Washington University School of Medicine in St. Louis.
Among the many genes linked to autism in people are six genes that attach a molecular tag called ubiquitin to proteins. These genes, called ubiquitin ligases, function like a work order, telling the rest of the cell how to deal with the tagged proteins: discarding, rerouting or dialing up or down.
Patients with autism may carry a mutation that prevents one of their ubiquitin genes from working properly.
To understand the role of ubiquitin genes in brain development, researchers at Washington University School of Medicine in St. Louis removed the ubiquitin gene RNF8 in neurons in the cerebellum of young mice, and found that neurons lacking the RNF8 protein formed about 50 percent more synapses, the connections that allow neurons to send signals from one to another, than those with the gene.
By measuring the electrical signal in the receiving cells, the researchers found that the strength of the signal was doubled in the mice that lacked the protein, which means the extra synapses worked.
Cerebellum is indispensable for movement and learning motor skills such as how to ride a bicycle. Some of the recognizable symptoms of autism, such as motor incoordination and a tendency to walk tippy-toed, involve control of movement.
The animals missing the RNF8 gene in the neurons of their cerebellum did not have any obvious problems with movement: They walked normally and appeared coordinated. But when the researchers tested their ability to learn motor skills, the mice without RNF8 failed miserably.
Then the researchers trained the mice to associate a quick puff of air to the eye with the blinking of a light. After a week of training, mice with a functioning copy of the gene closed their eyes in anticipation more than three quarters of the time, while mice without the gene shut their eyes just a third of the time.
Cerebellum is also important in higher cognitive functions such as language and attention, both of which are affected in autism. People with autism often have language delays and pay unusually intense attention to objects or topics that interest them. The cerebellum may be involved not only in motor learning but also in other features of autism as well, the researchers said.
"This study raises the possibility that there may be too many synapses in the brains of patients with autism," said senior author Azad Bonni, a professor of neuroscience and head of the Department of Neuroscience at Washington University School of Medicine in St. Louis. "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."
The study has been published in Nature Communications, an open access scientific journal published by the Nature Publishing Group.
