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Autism may begin at earliest brain development
Autism is not a single condition, but a spectrum of disorders that affect the brain's ability to perceive and process information. Recent research suggests that too many connections in the brain could be at least partially responsible for the symptoms of autism, from communication deficits to unusual talents.
New research from the University of Maryland (UMD) suggests that this overload of connections begins early in mammalian development, when key neurons in the cerebral cortex begin to first form circuits.
Researchers outline their findings in a paper published January 31, 2017 in the journal Cell Reports.
"Our work suggests that the neural pathology of autism manifests in the earliest cortical circuits, formed by a cell type called subplate neurons," said UMD Biology Professor and senior study author Patrick Kanold PhD.
"The cortex is a very important region in the adult human brain that undergoes a complex, multi-stage development process," said Daniel Nagode, a former postdoctoral researcher at UMD and lead author of the study. "Because our findings implicate the earliest stages of cortex circuit formation in a mouse model, they suggest that the pathological changes leading to autism might start before birth in humans."
To study the relationship between autism and subplate neuron development in mice, Kanold, Nagode and their collaborators injected the drug valproic acid (VPA) into mother mice on day 12 of their 20-day gestation. VPA has a known link to autism in humans and also induces autism-like cognitive and behavioral abnormalities in mice. While normal newborn mouse pups will emit frequent, high-pitched noises when they are separated from their littermates, VPA-treated pups do not.
Researchers then used a laser scanning photostimulation technique to map connections between individual subplate neuron cells in the brains of the mouse pups. Within the first week after birth, the VPA-dosed mice showed some patches of "hyperconnected" subplate neurons. In contrast, control mouse pups dosed with plain saline solution showed normal connections throughout their cortical tissue.
If the same dynamic plays out in human brains, hyperconnections in the developing cortex could result in the neural pathologies observed in human autism, Kanold said. In mice as well as in humans, the critical window of time when subplate neurons develop is very short.
"The timing of the effects is important. The hyperconnectivity in VPA pups occurs only in small patches a few days after birth," Nagode explains. "But after 10 days, the hyperconnectivity becomes much more widespread."
In mice, subplate neurons develop mostly after birth. Eventually, they die off and disappear, as other neural circuits take their place. However, in humans the first subplate neuron connections form in the second trimester. By the time of birth, most subplate neurons have already disappeared.
The research paper, "Abnormal development of the earliest cortical circuits in a mouse model of Autism Spectrum Disorder," Daniel Nagode, Xiangying Meng, Daniel Winkowski, Ed Smith, Hamza Khan-Tareen, Vishnupriya Kareddy, Joseph Kao, and Patrick Kanold, was published January 31, 2017 in the journal Cell Reports.
This work was supported by the National Institutes of Health (Award Nos. R01DC009607, R01GM056481, CEBHT32DC00046 and CEBHF32DC014887). The content of this article does not necessarily reflect the views of this organization.
University of Maryland
Subplate neurons form a network of interconnected scaffolding believed to support other neurons