Autism-related study discovers how drug interferes with neuronal cell function

July 7, 2010

A York University study has shown for the first time how the drug misoprostol, which has been linked to neurodevelopmental defects associated with autism, interferes with neuronal cell function.

It is an important finding because misoprostol is similar in structure to naturally-occurring prostaglandins, which are the key signaling molecules produced by in the brain.

Past clinical studies have shown an association between misoprostol and severe neurodevelopmental defects including autism symptoms. Those studies looked at cases in Brazil in which women misused the drug early in pregnancy in unsuccessful attempts to terminate their pregnancies.

The York study examined mouse neuronal cells to discover how the drug actually interferes at a molecular level with prostaglandins, which are important for development and communication of cells in the brain.

"Early in the first trimester of pregnancy, neuronal cells reach out to communicate with one another," says Dorota Crawford, an assistant professor in the School of Kinesiology & Health Science in York's Faculty of Health. "Our study shows that misoprostol interferes with this process by increasing the level of calcium ions in neuronal extensions, which reduces the number and length of these extensions. It prevents the cells from communicating with each other. If changes in prostaglandin level alter the development or differentiation of cells, it may have a physiological impact."

Crawford and Javaneh Tamiji, who undertook the research for her master's thesis in the Neuroscience Graduate Diploma Program at York, co-authored a study published online in the journal Biochemical and Biophysical Research Communications: "Prostaglandin E2 and misoprostol induce neurite retraction in Neuro-2a cells."

There is no indication that women in Canada are misusing misoprostol to terminate pregnancies, and in fact the drug is used safely for other purposes such as treatment and prevention of gastrointestinal ulcers. However, during early neuronal development the drug misoprostol or other environmental factors such as infections or inflammations, which can also increase the level of prostaglandins, may interfere with normal brain function, says Crawford.

Crawford and Tamiji focused on the drug misoprostol because they had evidence from the clinical studies of the neurotoxic effects of the drug. They used misoprostol and the naturally occurring prostaglandins side by side in their study and found that both compounds produced the same effects on function.

The study shows that misoprostol interferes with the prostaglandin pathway in a dose-dependent manner - in other words, the higher the dose, the greater the problems created.

"What that indicates to us is whether it is infection that will activate it, or whether it is the drug, it will cause the same effect," says Crawford.

Now that it has been shown that misoprostol affects interaction between cells, the next step will be to do animal studies on mice to examine the physiological impacts on particular parts of the , she says.

Crawford's lab is one of very few in the world that has adopted a multidisciplinary approach to the study of autism spectrum disorders, using molecular techniques to understand the link between causative biological factors (genes and environment) and the behavioural expression.

Related Stories

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.