Gene that guides earliest social behaviors could be key to understanding autism

 Little is known about how social behavior develops in the earliest stages of life. But most animals -- including humans -- are born with an innate ability to interact socially or form bonds with others. And that contributes to success throughout life.

Now, a new animal study points to a gene that is important for the earliest development of basic social behaviors.

The work also suggests that exposure to certain drugs and environmental risk factors during embryonic development can cause changes to this gene, leading to alterations in social behavior that are similar to those found in individuals who have autism. Much to their surprise, the researchers also found they could reverse some of the effects using an experimental drug.

"This study helps us understand at the molecular level why sociability is disrupted during the very earliest stages of life," says Randall T. Peterson, Ph.D., the corresponding author of the study and dean of the University of Utah College of Pharmacy. "It also gives us an opportunity to explore potential treatments that could restore sociability in these animals and, perhaps in time, eventually in humans as well."

More broadly, their findings suggest that the gene -- TOP2a -- controls a large network of genes that are known to increase the risk of autism. It also may serve as a link between genetic and environmental factors that contribute to onset of disorder, Peterson adds.

The study, conducted by University of Utah Health researchers and colleagues nationwide, appears in the Nov. 23 issue of Science Advances.

Anti-social animals

Scientists suspect many social traits are determined before birth. But the precise mechanisms involved in this process remain murky. One promising area of research suggests that social behavior and other characteristics and traits are influenced not only by our genetic makeup but also how and where we live.

To test this model, the scientists evaluated whether environmental exposures during embryonic development could influence social behavior. Peterson and his colleagues exposed zebrafish embryos to more than 1,100 known drugs -- one drug per 20 embryos -- for 72 hours beginning three days after conception.

The researchers determined that four of the 1,120 tested drugs significantly reduced sociability among the zebrafish. Fish exposed to these drugs were less likely to interact with other fish. It turned out that the four medications all belonged to the same class of antibiotics, called fluoroquinolones. These drugs are used to treat upper and lower respiratory tract infections in people.

When the scientists gave a related drug to pregnant mice, the offspring behaved differently when they became adults. Even though they appeared normal, they communicated less with other mice and engaged in more repetitive acts -- like repeatedly poking their head in the same hole -- than other rodents.

A basis for sociability

Digging deeper, the researchers found that the drugs suppressed a gene called TOP2a, which, in turn, acted on a cluster of genes that are known to be involved in autism in humans.

They also found that the cluster of autism-associated genes shared another thing in common -- a higher than usual tendency to bind a group of proteins called the PRC2. The researchers hypothesized that Top2a and the PRC2 work together to control the production of many autism-associated genes.

Source: ScienceDaily