Team finds possible autism targets in brain

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Thursday, February 19, 2009

A team of Brown neuroscience researchers have discovered a new potential target in the fight against autism.

Michael Akins and Sean Christie, postdoctoral research fellows in neuroscience, were the lead authors in a study published this month in the Journal of Neuroscience that reports the discovery of tiny molecular bodies, dubbed “Fragile X granules,” that appear in developing neural circuits.

For years, scientists have known that autism is a disease involving chemical communication in the brain, and have experimented on the postsynaptic side of neural connections, said Professor of Medical Science Justin Fallon, the senior author of the study.

But the Brown research team, which also included a Tufts University scientist, explored the presynaptic side of these connection as well, showing that the so-called “Fragile X” gene, important in brain development, was expressed in those locations, too.

Examining slices of rodent brain tissue with electron microscopes, the scientists not only identified Fragile X proteins in some presynaptic terminals, but discovered them in tiny granules floating around brain cells – which likely contain RNA, the messenger molecules cells use to express genes.

James Schwob, the Tufts professor of anatomy and cellular biology who contributed to the study, said he concentrated on the regeneration of the brain’s olfactory system, since it is the only part of the nervous system capable of a certain kind of regeneration.

The pattern and expression of the Fragile X granule, Schwob said, suggested it was located on the presynaptic side. The study also showed that the granules exist in at least the frontal cortex, hippocampus and olfactory bulb of the brain.

The Fragile X granule is an appealing target in the development of therapies geared toward autism, Fallon said. This discovery gives rise to the possibility that “Fragile X is going to be a niche player,” he said. “This is going to help us illuminate how these genes work together functionally.”

The study also implies that these granules may be able to provide “insight into potential disease mechanisms,” Akins said. The identification of the Fragile X granule is just the first of many steps toward understanding the proteins expressed by the Fragile X gene, he said.

“It is very provocative where we see these granules,” he said.

Experimentation and analysis will continue so the specific function of the Fragile X granules can be pinpointed, he added.

“We don’t have any evidence that they are functionally involved in the circuits but we have indication that they may be,” Fallon said. As a result, he said, the researchers are now trying to discover what the proteins do and how they are regulated.

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