Genes that guide early social behavior may 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 the ability to
interact socially or connect with others.
This contributes to a lifetime of success
.

Now, a new animal study points to a gene
important for the early development of basic social behavior.

The study also showed that exposure to certain drugs and environmental risk factors during embryonic development leads to changes in the gene that lead to changes in social behavior similar to those found in people with autism
.
To their surprise, the researchers also found that they could reverse some of the effects
by using an experimental drug.

"This study helps us understand at the molecular level why social competence is disrupted in the earliest stages of life," said Randall T.
Peterson, Ph.
D.
, corresponding author of the study and dean of the University of
Utah's School of Pharmacy.
"It also gives us the opportunity to explore potential treatments that could restore social abilities in these animals and, eventually, in humans
.
"

More broadly, their findings suggest that this gene — top2a — controls a network
of genes known to increase autism risk.
It may also be a link between genetic and environmental factors that contribute to the occurrence of the disease, Peterson added
.

The study, conducted by health researchers at the University of Utah and colleagues across the country, was published Nov.
23 in Scientific Advances
.

Antisocial animals

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

To test this model, the scientists assessed whether environmental exposures during embryonic development affected social behavior
.
Peterson and his colleagues exposed zebrafish embryos to more than 1,100 known drugs — one in every 20 embryos — for 72 hours
starting 3 days after conception.

The researchers determined that four of the 1120 drugs tested significantly reduced the sociability
of zebrafish.
Fish exposed to these drugs are less likely to interact
with other fish.
It turned out that all four drugs belonged to the same class of antibiotics, called fluoroquinolones
.
These drugs are used to treat infections of the upper and lower respiratory tract in people
.

When the scientists administered a related drug to pregnant mice, their offspring behaved differently
as adults.
Although they look normal, they communicate less with other mice than other rodents and engage in more repetitive behaviors — such as repeatedly sticking their heads into the
same hole.

The basis of socializing

After digging deeper, the researchers found that the drugs suppressed a gene called TOP2a, which in turn acts on a group of genes
known to be associated with autism in humans.

They also found that this group of autism-related genes also had in common — a higher-than-usual tendency to bind to a group of proteins called PRC2
.
The researchers speculate that Top2a and PRC2 together control the production
of many autism-related genes.

To determine whether antisocial behavior could be reversed, the team administered embryonic and juvenile zebrafish an experimental drug called UNC1999, which is known to inhibit PRC2
.
After receiving medication, fish exposed to fluoroquinolones were more likely to swim closer to other fish, suggesting that the drug helped restore social skills
.
They saw similar results
on other drugs known to inhibit the same key gene, TOP2a.

"It really surprised me because I thought it was irreversible to interfere with brain development during the embryonic period
," Peterson said.
"If you don't develop sociality in the embryonic years, you're missing out on a window
of opportunity.
But this study shows that even in the later years of these people, you can still inhibit this pathway and return to socializing
.
”

As a next step, the researchers plan to explore how and why the drug produces this effect
.

Although scientists have found only four compounds to be Top2a inhibitors, evidence suggests that there are hundreds of other drugs and naturally occurring compounds in our environment that can inhibit its activity
.

"It's possible that these four compounds are just the tip
of the iceberg of potentially problematic substances in embryonic exposure," Peterson said.

However, Peterson noted that the study was conducted in animals, and more research
is needed before its results can be confirmed in humans.
Therefore, he cautions against jumping to conclusions
about real-world applications.

"We have no evidence that fluoroquinolones or any other antibiotics cause autism in humans," Peterson said
.
"Therefore, there is no reason to stop using antibiotics
.
The paper identifies a new molecular pathway that appears to control social development and deserves further exploration
.
”