Autism link of the day - tuberous sclerosis complex

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A team of Michigan State researchers discovered a connection between the rare disease tuberous sclerosis complex, or TSC, and autism and epilepsy.

The correlation connects the three disorders to the mutation of two different genes that result in the restraint of proteins that are related to multiple disorders with high rates of autism.

WHAT IS TUBEROUS SCLEROSIS COMPLEX?

TSC affects multiple organ systems, causing benign tumors to grow on the skin, heart, kidneys and lungs.

It was known prior that there were high rates of people with TSC also having autism and seizures, but the study — published in Nature Communications — focuses on mutations in two specific genes that are critical to the pathway that retrains a protein often correlated with high rates of autism.

Around 90% of all people with TSC have seizures and about half have autism spectrum disorder.

When the two genes mutate, they turn off the protein mammalian target of rapamycin, or mTOR. When the mutation results in mTOR activating at the wrong times, people develop autism.

mTOR regulates the development and function of brain cells, and understanding how the protein works is crucial in understanding its role in the development in autism and neuropsychiatric symptoms of TSC because the study proved how crucial the protein is in the pathway.

HOW THE RESEARCH CAME ABOUT

The team made the breakthrough when they were working with inhibitory neurons in the brain and their properties. Inhibitory neurons release the neurotransmitter gamma aminobutyric acid, or GABA, whereas excitatory neurons release the neurotransmitters epinephrine and norepinephrine.

“That was kind of a shock, we didn’t really expect that at all,” author and assistant professor in the College of Human Medicine’s Department of Pediatrics and Human Development Daniel Vogt said. “For the field, it was kind of a big deal because we have been trying to understand what gives these inhibitory cells their properties to begin with.”

In many humans and animals on the autism spectrum, the group of cells that the research team was working with took on properties of other cells. The group of cells for people with autism are usually altered, Vogt said.

“We had a cell type that just kind of turned on properties in an unexpected way,” Vogt said. “Correlating with that, we also had the inhibitory neurons that we affected were less excitable. In other words, the brain itself had less inhibition which we think might also contribute to seizures in this disorder.”

The researchers followed a pathway of genes that worked similarly to an assembly line — if something along the line is faulty, people can develop diseases and disorders.