A new study from OMRF has found that worms with an autism-related mutation are more susceptible to environmental toxins such as mercury, copper and paraquat.
The researchers also found that the animals, which lacked a protein in the nervous system known as neuroligin, displayed sensory problems like those found in individuals with autism spectrum disorders.
OMRF researchers James Rand, Ph.D., Gregory Mullen, Ph.D., and Jerrod Hunter published their findings this month in the journal Disease Models and Mechanisms.
Starting in 2003, a series of studies showed that some individuals with autism have mutations in genes that give rise to proteins called neuroligins. Neuroligins are important components of synapses, the sites of direct chemical communication between nerve cells. Using tiny roundworms whose nervous systems are surprisingly similar to those in humans, the OMRF researchers created a strain of worms that lacked neuroligin.
The scientists found that these animals exhibited higher levels of “oxidative stress,” which is caused by an excess of highly reactive oxygen molecules known as free radicals. Different types of oxidative stress have been linked to numerous diseases in humans, including heart failure, ALS and Alzheimer’s disease.
“This was a completely unexpected result,” said Rand, who holds the H.A. and Mary K. Chapman Chair in Medical Research at OMRF and was the senior author on the paper. “We didn’t expect a mutation that affects how nerve cells communicate to have anything to do with oxidative stress.”
The worms also exhibited a heightened sensitivity to the toxic effects of agents that cause or increase oxidative stress. Such agents include heavy metals such as mercury and copper, as well as the herbicide paraquat.
The worms had specific sensory deficits, similar to those frequently reported in individuals with autism. “Worms without neuroligin performed differently in tests than those with the protein,” Rand said. “They didn’t react to certain smells or changes in temperature that would affect normal worms.”
There have been a number of published reports indicating a correlation between some cases of ASDs and increased oxidative stress, but in Rand’s mutant worms, the loss of neuroligin is actually the cause.
“If a comparable mechanism exists in humans, it is possible that autism spectrum disorders might be the cause, rather than the result, of oxidative stress,” he said.
Although his results are clearly suggestive, Rand cautions not to read too much into them just yet. “There’s a lot more work to be done before we start linking what happens in worms in a laboratory to human neurological disorders.”
Rand said his lab will continue looking for the precise mechanism that leads from a mutation in the nervous system to oxidative stress, in hopes that it will provide a framework for future studies using mice and, perhaps eventually, individuals with autism.
The research was funded by a grant from Autism Speaks and by the Oklahoma Medical Research Foundation.
About Autism Spectrum Disorders
Autism spectrum disorders (ASDs) include a range of developmental brain disorders that affect social interaction, communication and learning. The prevalence of these disorders is increasing, and according to a recent report from the Centers for Disease Control and Prevention (CDC), ASDs now affect approximately 1 in every 110 children (http://www.cdc.gov/ncbddd/autism/data.html ). ASDs are caused by a combination (and/or interaction) of multiple genetic and environmental factors; information about diagnosis and treatment may be found at the National Institutes of Health (http://www.ninds.nih.gov/disorders/autism/detail_autism.htm).
