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    Categories: Science

Brain Connection: Cause of Autism

Reported Findings

The Breakthrough

Scientists have recently reported findings that could be a new breakthrough in autism research in the November 2, 2017, issue of the science journal “Nature Communications.” They conducted a study at the Washington University School of Medicine that demonstrated that autism might be caused by an overabundance of synapses or connections within the brain. Far from improving the brain’s function, the extra synapses cause communication problems within the nervous system that lead to confusion in the brain.

Neuroscientist Explanation Simplified

Dr. Azad Bonni, the lead author and the head of the Department of Neuroscience at Washington University, explained that too many brain synapses interfere with the neurons’ ability to communicate with each other effectively. An excessive number of neurons within the developing brain causes some learning disabilities. Dr. Bonni admits that the researchers have not yet determined how the excessive number of synapses impair the brain.

1 out of Every 68 Children 

Autism, more formally called “autism spectrum disorder,” is a common developmental disorder that affects about one out of every 68 children in the United States. It is a life-long condition that causes language and social problems. Autism is called a “spectrum disorder,” because patients vary widely in their level of disability. Some have mild cases and can lead fairly normal lives, while others are severely disabled and need constant care. Scientists have long believed that environmental and/or genetic factors may cause autism.

The RNF8 Gene’s Link to Autism

Synapses Overload

Several genes have been linked to autism. One of them, the RNF8 gene, is responsible for regulating the synapses or connections between neurons. The synapses let the neurons communicate with each other. A defective RNF8 gene causes the formation of too many synapses that overload the nervous system within the brain. Scientists believe that overload may be one of the causes of autism.

Removal of the RNF8 Gene

The researchers at Washington University wanted to see what would happen if they completely removed the RNF8 gene from the cerebellum of juvenile rats and mice. The cerebellum controls motor skills and cognitive functions like language. It is also one of the parts of the brain affected by autism. While autism is best known for its effects on a patient’s social and language skills, it also affects their motor skills. Many people with autism are uncoordinated and have a tendency to walk on their tip-toes.

The scientists observed that the neurons in the mice with no RNF8 gene formed 50 percent more synapses than did the neurons in mice with the gene. Those extra synapses did work. The researchers measured the electrical signal in the receiving cells and found it was twice as strong as the signal in normal mice.

No RFN8 Findings

The mice without the RNF8 gene also displayed normal motor skills; they could walk normally, for example. Tests, however, showed that they had marked difficulty learning new motor skills. In one test, the scientists trained the mice to associate a blinking light with an oncoming puff of air directed at their eyes. Normal mice soon learned to close their eyes when they saw the light blink to avoid getting an annoying air puff in their eyes. After a week of training, the normal mice closed their eyes about 75 percent of the time, but the mice with no RFN8 gene closed their eyes only about 33 percent of the time.

Dr. Bonni stated that more research is needed to determine if an excessive number of synapses causes autism in humans. If it does, scientists can work on ways to regulate the number of synapses.

Other Genes Linked to Autism

RNF8 is 1 out of 6 Genes

RNF8 is one out of six genes called ubiquitin ligases. Their job is to attach ubiquitin, a molecular tag, to proteins. The genes use the tags as work orders that instruct the rest of the cell on what to do with a given protein: Discard it, adjust its activity level, or send it to another part of the cell. Since publishing the original paper, Dr. Bonni and his team have found that removing or inhibiting any of the ubiquitin ligases causes rodents to develop an abnormally high number of synapses.

Enhanced Brain Power Genes Linked to Autism

Scientists have also been researching genes that seem to enhance brain power and are linked to autism. One study done earlier this year demonstrated that genetic mutations linked to autism might be passed down from one generation to the next. Such genes survive the evolutionary processes that eliminate the genes that cause negative effects. Genes which cause autism survive, however, because they also enhance cognitive abilities like decision-making skills.

Related Research

Brain Tissue Analysis

Earlier this year, researchers at the Columbia University Medical Center conducted postmortem analyses of brain tissues from children with autism and compared them with brain tissue taken from normal children. Dr. Guomei Tang from Columbia analyzed cortical tissue from the children’s brains and found that children with autism had had significantly more synapses than normal children.

Cause of Excess or Defective Synapses

During fetal development, synapses go through a process called “autophagy” that prunes the excess. A protein called mTOR controls the process. A person with autism has overactive mTOR that prevent autophagy from occurring and disposing of excess or defective synapses.

What is Next

Plans for the Future

The study published in “Nature Communications” discusses the possibility of preventing the excess synapses from developing between the neurons. That can also provide methods of regulating the connectivity between the neurons as new synapses form. For example, it might prevent new synapses from forming for no obvious reason, as in when the patient does not learn a new skill.

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