UCLA. US: People with autism spectrum disorders have difficulty with social
behavior and communication, which can make it challenging to form
friendships, engage in routine conversations or pick up on the social
cues that are second nature to most people. Similarly, mice with
symptoms of autism show little interest in interacting or socializing
with other mice. A drug called risperidone has been shown to treat some symptoms of
autism — including repetitive behaviors — in both humans and mice, but
so far no medication has been found to help improve the ability to
socialize.
In a study published online by the journal Science Translational
Medicine, researchers at UCLA found that giving oxytocin to mice with
autism-like symptoms restored their normal social behavior. Oxytocin is a
neuropeptide, a type of molecule that helps neurons communicate with
one another.
But perhaps the study’s biggest surprise was that early postnatal
administration of the oxytocin led to longer-lasting positive effects,
which continued into the animals’ adolescence and adulthood. “This
suggests that there may be critical windows of time for treatment that
are better than others,” said Daniel Geschwind, a UCLA professor of
psychiatry, neurology and human genetics and senior author of the study.
In 2011, Geschwind and his colleagues developed a mouse model
for autism spectrum disorders by knocking out a gene called
contactin-associated protein-like 2, or CNTNAP2, which scientists
believe plays an important role in the brain circuits responsible for
language and speech. Previous research has linked common CNTNAP2
variants to a heightened risk for autism, while rare variants can lead
to an inherited form of autism called cortical dysplasia-focal epilepsy
syndrome.
“The oxytocin system is a key mediator of social behavior in mammals,
including humans, for maternal behavior, mother–infant bonding, and
social memory,” said Geschwind, who holds UCLA’s Gordon and Virginia
MacDonald Distinguished Chair in Human Genetics and is the director of
the Center for Autism Research and Treatment at the Semel Institute for
Neuroscience and Human Behavior at UCLA. “So it seemed like a natural
target for us to go after.”
The mice that were engineered for autism have fewer oxytocin neurons
in the hypothalamus than other mice and lower-than-normal oxytocin
levels throughout the brain. But after researchers treated them with
oxytocin, the animals spent normal amounts of time interacting with
other mice — the measure scientists used to gauge their sociability.
Separately, the researchers gave the mice melanocortin, an agonist
that binds to specific receptors on a cell in order to activate it. They
found that it caused a natural release of oxytocin from the mice’s
brain cells, which also improved the mice’s sociability.
“The study shows that a primary deficit in oxytocin may cause the
social problems in these mice, and that correcting this deficit can
correct social behavior,” Geschwind said.
The next stage of the research, Geschwind said, will be to determine
the lowest dosage of oxytocin that still proves effective. Because the
mice in the study displayed symptoms similar to those of people on the
autism spectrum, the researchers hope that this therapy may someday be
applicable to humans.
The study was funded by the National Institute of Mental Health (R01
MH081754-02R, NIH/NS50220), the NIH Autism Centers of Excellence
(HD055784-01 and 5R01-MH081754-04), the Simons Foundation Autism
Research Initiative, Autism Speaks (7657), the NIH/National Institute of
Neurological Disorders and Stroke (R01 NS049501 and R01 NS074312) and a
McKnight Foundation Brain Disorders Award.
The study’s other authors were Olga Peñagarikano, María Lázaro,
Xiao-Hong Lu, Hongmei Dong, Hoa Lam, Elior Peles, Nigel Maidment, Niall
Murphy and X. William Yang, all of UCLA; Peyman Golshani of UCLA and the
West Los Angeles V.A. Medical Center; and Aaron Gordon of Israel’s
Weizmann Institute of Science.