TORONTO, Ontario, Canada, April 9, 2014 (ENS) – Autism can be triggered by abnormal levels of lipid molecules in the brain that affect the interaction between two key neural pathways in early brain development in the womb, researchers at York University have learned.
The scientists discovered that environmental causes such as exposure to chemicals in some cosmetics and common over-the-counter medications can affect the levels of these lipids.
Autism is a primary disorder of brain development with symptoms ranging from mild to severe and including repetitive behavior, deficits in social interaction, and impaired language. It is four times more prevalent in boys than in girls and the incidence continues to rise.
The U.S. Center for Disease Control and Prevention estimates that 1 in 68 children now has autism, based on data from 2010.
“We have found that the abnormal level of a lipid molecule called Prostaglandin E2 in the brain can affect the function of Wnt proteins. It is important because this can change the course of early embryonic development,” explained Professor Dorota Crawford in the Faculty of Health and a member of the York Autism Alliance Research Group.
Prostaglandin E2 (PGE2) is a bioactive fatty acid, a natural lipid-derived molecule involved in healthy, normal functioning of the human body. The York University researchers write, “Abnormal PGE2 signalling has been associated with pathologies of the nervous system.”
This is the first time research shows evidence for “cross-talk” between PGE2 and Wnt signalling in neuronal stem cells, according to the peer reviewed study published Monday in the journal “Cell Communication and Signaling,”
“Extracellular stimuli such as immunological and infectious agents, environmental toxins such as mercury and lead, and exposure to drugs including misoprostol and valproic acid can trigger the local production of PGE2 via specific biosynthetic pathways, resulting in altered cell signal transmission that modulates biological functions such as sleep, fever, inflammation, and pain,” the authors state.
In addition, the study states, “Increasing evidence for the contribution of environmental factors in the etiology of neurodevelopmental disorders like ASD [autism spectrum disorder] has prompted urgency to reveal their potential exogenous causes and underlying mechanisms.”
“Environmental factors like exposure to drugs, toxins or infectious agents cause disruptions in PGE2 signalling by increasing the levels of oxidative stress, consequent lipid peroxidation, and the immunological response; these factors and consequences that disturb normal PGE2 signalling have all been linked to ASD,” the study states.
Lead researcher and York University doctoral student Christine Wong said, “Using real-time imaging microscopy, we determined that higher levels of PGE2 can change Wnt-dependent behavior of neural stem cells by increasing cell migration or proliferation. As a result, this could affect how the brain is organized and wired.”
“Moreover, we found that an elevated level of PGE2 can increase expression of Wnt-regulated genes — Ctnnb1, Ptgs2, Ccnd1, and Mmp9. “Interestingly, all these genes have been previously implicated in various autism studies,” said Wong.
According to Crawford, genes do not undergo significant changes in evolution, so even though genetic factors are the main cause, environmental factors such as insufficient dietary supplementations of fatty acids, exposures to infections, various chemicals or drugs can change gene expression and contribute to autism.
“The statistics are alarming. It’s 30 percent higher than the previous estimate of 1 in 88 children, up from only two years earlier. Perhaps we can no longer attribute this rise in autism incidence to better diagnostic tools or awareness of autism,” said Crawford.
“It’s even more apparent from the recent literature that the environment might have a greater impact on vulnerable genes, particularly in pregnancy. Our study provides some molecular evidence that the environment likely disrupts certain events occurring in early brain development and contributes to autism.”
There is no cure for autism, according to the Centers for Disease Control and Prevention, which acknowledges possible environmental causes. “We do not know all of the causes of ASD. However, we have learned that there are likely many causes for multiple types of ASD,” says the CDC on its website. “There may be many different factors that make a child more likely to have an ASD, including environmental, biologic and genetic factors.”
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