Brian Sullivan
Autism may be caused by misconnections in the developing brain opening the possibility of a future Autism and thdrug treatment published in Nature Neuroscience on January 10.
Researchers from Children's Hospital Boston looked at a rare disorder called tuberous sclerosis complex (TSC), which causes benign tumors throughout the body, including the brain. Most individuals with TSC also develop epilepsy, and 25–50% are diagnosed with autism spectrum disorders.
The study found that mutations in one of TSC's causative genes (TSC2) prevent growing nerve fibers (axons) from locating their proper targets in the developing brain.
According to researchers at, it may be possible to one day treat the problem with drugs that target the molecular pathways that cause the miswiring.
Advances in recent have suggested that “dysregulation of axon growth and guidance is important in the pathogenesis of epilepsy, autism and intellectual disabilities.”
“ Deficient axonal growth has been associated with cerebral dysgenesis and intellectual disability” noted the study, “ whereas excessive growth of neuronal processes has been associated with epilepsy.”. The role of neuronal connectivity has also become apparent in autism. “
Magnetic resonance imagery has shown that autistic individuals had increased white-matter volume and aberrant white matter adjacent to brain regions implicated in social cognition.
The team focused on an axon route between the eye's retina and the brains visual processing area in mice. In neurons deficient in TSC2, the axons' tips, called growth cones, did not respond to cues from ephrin miolecules and the axons ended up in the wrong locations..
"Normally, ephrins cause growth cones to collapse in neurons, but in tuberous sclerosis the axons don't heed these repulsive cues, so keep growing," senior investigator Dr. Mustafa Sahin.
When neurons are deficient in TSC2, a molecular pathway called mTORis activated resulting in a loss of axon responsiveness to ephrin signals.




Supporting the mouse data, Sahin and his colleague Simon Warfield, from the Computational Radiology Laboratory examined the brains of 10 patients with TSC, 7 of whom also had autism or developmental delay, and 6 unaffected controls.
Using diffusion tensor imaging they documented disorganized and structurally abnormal tracts of axons in the TSC group, particularly in the visual and social cognition areas of the brain (see image).
They found the axons were poorly myelinated., That means the fatty coating that helps conduct electrical signals was compromised
In the images above the brighter images in the healthy brain apear brighter.because of the structural integrity allowing electrical flow. Sahin said their findings may help improve our general understanding of how the developing brain organizes.

"People have started to look at autism as a developmental disconnection syndrome -- there are either too many connections or too few connections between different parts of the brain" said Sahin.
"In the mouse models, we're seeing an exuberance of connections, consistent with the idea that autism may involve a sensory overload, and/or a lack of filtering of information."
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