Some neuroscientists feel that autism might be a developmental disconnection syndrome: there are either too many connections or too few connections between different parts of the brain. In the mouse models there is an excess of connections suggesting that autism may involve a sensory overload or a lack of filtering of sensory information. Many of the genes implicated in autism seem to be controlling the wiring of nerve cells.
There are plans in the works to start a clinical trial of a drug that targets the brain's miswiring in hopes that it can improve autistic symptoms since a similar drug in animals controlled the abnormal axonal proliferation.
ScienceDaily (Jan. 11, 2010) — Studying a rare disorder known as tuberous sclerosis complex (TSC), researchers at Children's Hospital Boston add to a growing body of evidence suggesting that autism spectrum disorders, which affect 25 to 50 percent of TSC patients, result from a miswiring of connections in the developing brain, leading to improper information flow. The finding may also help explain why many people with TSC have seizures and intellectual disabilities.
TSC causes benign tumors throughout the body, including the brain. But patients with TSC may have autism, epilepsy or intellectual disabilities even in the absence of these growths. Now, researchers led by Mustafa Sahin, MD, PhD, of Children's Department of Neurology, provide evidence that mutations in one of the TSC's causative genes, known as TSC2, prevent growing nerve fibers (axons) from finding their proper destinations in the developing brain.
Studying a well-characterized axon route -- between the eye's retina and the visual area of the brain -- Sahin and colleagues showed that when mouse neurons were deficient in TSC2, their axons failed to land in the right places. Further investigation showed that the axons' tips, known as "growth cones," did not respond to navigation cues from a group of molecules called ephrins. "Normally ephrins cause growth cones to collapse in neurons, but in tuberous sclerosis the axons don't heed these repulsive cues, so keep growing," says Sahin, the study's senior investigator.
Additional experiments indicated that the loss of responsiveness to ephrin signals resulted from activation of a molecular pathway called mTOR, whose activity increased when neurons were deficient in TSC2. Axon tracing in the mice showed that many axons originating in the retina were not mapping to the expected part of the brain.
More Evidence That Autism Is a Brain 'Connectivity' Disorder
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