People with autism spectrum disorder often experience a period of accelerated brain growth after birth. No one knows why, or whether the change is linked to any specific behavioral changes.

A new study by UCLA researchers demonstrates how, in pregnant mice, inflammation, a first line defense of the immune system, can trigger an excessive division of neural stem cells that can cause "overgrowth" in the offspring's brain.

The paper appears Oct. 9 in the online edition of the journal Stem Cell Reports.

"We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals," said Dr. Harley Kornblum, the paper's senior author and a director of the Neural Stem Cell Research Center at UCLA's Semel Institute for Neuroscience and Human Behavior.

In the study, the researchers mimicked environmental factors that could activate the immune system -- such as an infection or an autoimmune disorder -- by injecting a pregnant mouse with a very low dose of lipopolysaccharide, a toxin found in E. coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged the offspring's' brains.

Neural stem cells become the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect them.

Notably, the researchers found that mice with enlarged brains also displayed behaviors like those associated with autism in humans. For example, they were less likely to vocalize when they were separated from their mother as pups, were less likely to show interest in interacting with other mice, showed increased levels of anxiety and were more likely to engage in repetitive behaviors like excessive grooming.

Kornblum, who also is a professor of psychiatry, pharmacology and pediatrics at the David Geffen School of Medicine at UCLA, said there are many environmental factors that can activate a pregnant woman's immune system.

"Although it's known that maternal inflammation is a risk factor for some neurodevelopmental disorders such as autism, it's not thought to directly cause them," he said. He noted that autism is clearly a highly heritable disorder, but other, non-genetic factors clearly play a role.

The researchers also found evidence that the brain growth triggered by the immune reaction was even greater in mice with a specific genetic mutation -- a lack of one copy of a tumor suppressor gene called phosphatase and tensin homolog, or PTEN. The PTEN protein normally helps prevent cells from growing and dividing too rapidly. In humans, having an abnormal version of the PTEN gene leads to very large head size or macrocephaly, a condition that also is associated with a high risk for autism.

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Neural stem cell overgrowth, autism-like behavior linked, mice study suggests

Chuck Bednar for redOrbit.com Your Universe Online

Researchers writing in the October 9 edition of the journal Cell report they have for the first time successfully converted human embryonic stem cells into insulin-producing beta cells equivalent in nearly every way to regular, normally-functioning beta cells.

The discovery, which was the work of a team led by Douglas Melton of the Harvard University Department of Stem Cell and Regenerative Biology and the Howard Hughes Medical Institute, is being hailed as a breakthrough in the search for an effective way to treat type 1 diabetes a disease which affects an estimated three million Americans each year.

According to BBC News online health editor James Gallagher, Melton and his colleagues were able to produce hundreds of millions of the cells in their laboratory. Furthermore, their tests on mice demonstrated that the cells could treat the disease, which is caused when the immune system begins destroying the cells that are responsible for controlling blood glucose levels.

Beta cells in the pancreas pump out insulin to bring down blood sugar levels, Gallagher said. But the bodys own immune system can turn against the beta cells, destroying them and leaving people with a potentially fatal disease because they cannot regulate their blood sugar levels. It is different to the far more common type 2 diabetes.

Melton, who started his search for a cure for type 1 diabetes when his infant son Sam was diagnosed with the disease 23 years ago, said that he hopes to start human transplantation trials using the cells within a few years time. The professor, whose daughter also has type 1 diabetes, said in a statement that his team is now just one preclinical step away from the finish line.

The breakthrough comes after 15 years of seeking a bulk recipe for making beta cells, which sense the level of sugar in the blood and keep it in a healthy range by making precise amounts of insulin, said John Lauerman of Bloomberg Businessweek. He added that the technique, which begins with human stem cells, which have the ability to become any type of tissue or organ, is an important step toward understanding and treating diabetes.

This is part of the holy grail of regenerative medicine or tissue engineering, trying to make an unlimited source of cells or tissues or organs that you can use in a patient to correct a disease, added Albert Hwa, director of discovery science at JDRF, a New York-based type 1 diabetes research group that funded Meltons work.

The Harvard researcher explained to Lauerman that their research has led to the development of a six-step recipe for making mature, insulin-secreting beta cells that takes 30 days. He added that laboratories will be able to use the cells to test drugs to treat type 1 diabetes, as well as to gain new insight as to how the disease originally occurs.

In addition, since the researchers successfully manufactured the millions of beta cells required for transplantation, Telegraph Science Editor Sarah Knapton said that it could spell the end of daily insulin injections for the 400,000 type 1 diabetes patients in the UK and the over 30,000 Americans newly diagnosed with the disease each year.

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Stem Cell Breakthrough Brings Researchers One Step Closer To Type 1 Diabetes Cure