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Antidepressant Alleviates Autism-Like Symptoms in Mice

PET imaging in mice brains reveals changes in glucose consumption, which tracks alterations in neural signaling. | RIKEN/ Nippon Medical School

The FDA-approved drug fluoxetine, also known by the brand name Prozac, restored levels of a key neurotransmitter and improved behavior in mice with an autism-like disorder, a new study in the June 21 issue of Science Advances reports.

The drug restored in the mice normal levels of serotonin, a neurotransmitter communicating messages between nerve cells in the brain. Scientists still have much to learn about serotonin's role in autism spectrum disorder, though previous studies have suggested a link between low levels of the neurotransmitter and ASD symptoms.

Further research on how serotonin works in the human brain is needed, according to study author Dr. Toru Takumi, a senior team leader at the RIKEN Brain Science Institute in Japan, to determine whether drugs like fluoxetine could offer similar potential to treat humans with ASD.

"Antidepressant use during pregnancy is a controversial issue. We don't claim our study can simply be applied to clinical cases," Takumi said. "Before that, it's important to precisely understand the function of serotonin or serotonergic neurons during [human] neural development."

About one in 68 children in the United States are identified as having ASD , according to the Centers for Disease Control and Prevention.

In mouse models of ASD, symptoms include an imbalance between "on" and "off" neural signaling in the brain's neocortex, altered responses to sensory stimuli and impaired social behavior.

It is hard to distinguish the ASD-model mice from normal mice at a glance, though the model mice look more anxious, said Takumi.

To examine the mice's social interaction and brain activity, Takumi and the team of scientists studied electrical activity between neurons in their brain, performed behavioral tests — measuring calls between the mice, for example — and analyzed brain scans.

The scientists administered fluoxetine to the ASD-like mice after birth, through their mother's breast milk. In some cases, the offspring were treated with the drug directly, after weaning.

Early treatment with the drug may allow it to correct some impairment in neural development that contributes to ASD-like behavior in mice, the researchers said.

They found that treatment reversed some ASD-like symptoms in the adult offspring; namely, it improved social interactions and restored the balance between "on" and "off" signaling in the cortex.

Future studies should investigate whether, or how, the genetic alterations that lead to this ASD animal model change the serotonin system, with the aim to provide possible insight into serotonergic deficits in human patients, the authors say.

[Credit for related image: Flickr/ nuwandalice/ CC BY-NC_ND 2.0]