Serotonin is a brain chemical that carries signals across the synapse, or gap between nerve cells. The supply of serotonin is regulated by the serotonin transporter (SERT). In 2005, a team of Vanderbilt researchers led by Randy Blakely and James Sutcliffe identified rare genetic variations in children with ASD that disrupt SERT function.
In a new study published this week in the Proceedings of the National Academy of Sciences (PNAS), the researchers report the creation of a mouse model that expressed the most common of these variations.
The change is a very small one in biochemical terms, yet it appears to cause SERT in the brain to go into "overdrive" and restrict the availability of serotonin at synapses.
"The SERT protein in the brain of our mice appears to exhibit the exaggerated function and lack of regulation we saw using cell models," said Blakely, director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research.
"Remarkably, these mice show changes in social behavior and communication from early life that may parallel aspects of ASD," noted first author Jeremy Veenstra-VanderWeele, assistant professor of Psychiatry, Pediatrics and Pharmacology.
The researchers conclude that a lack of serotonin during development may lead to long-standing changes in the way the brain is "wired."
In 1961, investigators at Yale discovered that as many as 30 percent of children with autism have elevated blood levels of serotonin, a finding described as "hyperserotonemia."
Since then, these findings have been replicated many times. Indeed, hyperserotonemia is the most consistently reported biochemical finding in autism, and is a highly inherited trait. Yet, the cause or significance of this "bio-marker" has remained shrouded in mystery.
Until now. In the current study, Veenstra-VanderWeele, Blakely and their colleagues showed that they could produce hyperserotonemia in mice that express a variant of a human SERT gene associated with autism.
Because the genetic change makes the transporter more active, higher levels of serotonin accumulate in platelets and therefore in the bloodstream. In the brain, overactive transporters should have the opposite effect – lowering serotonin levels at the synapse and producing behavioral changes relevant to autism. That's exactly what the researchers observed.
Of course, no mouse model can completely explain or reproduce the human condition. Neither does a single genetic variation cause autism. Experts believe the wide spectrum of autistic behaviors represents a complex web of interactions between many genes and environmental factors.
But animal models are critical to exploring more deeply the basis for the developmental changes that are observed in ASD. The scientists are using these mice to explore how altered brain serotonin levels during development may produce long-lasting changes in behavior and impact the risk for autism.
Scientists from the National Institute of Mental Health, the Medical University of South Carolina and the University of Texas Health Science Center in San Antonio contributed to the study.
The research was supported by the National Institutes of Health, the advocacy organization Autism Speaks and the American Academy of Child and Adolescent Psychiatry.
Bill Snyder | EurekAlert!
New system for widespread availability of green hydrogen
26.05.2020 | Technische Universität Graz
When predictions of theoretical chemists become reality
22.05.2020 | Technische Universität Dresden
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.
A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...
By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.
Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...
Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale
Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
25.05.2020 | Medical Engineering
25.05.2020 | Information Technology
25.05.2020 | Information Technology