Scientists Discover Origin of Wide Range of Brain Disorders

A mechanism that guides the exquisite wiring of neural circuits in a developing brain-gaining unprecedented insight into the faulty circuits that may lead to brain disorders ranging from autism to mental retardation has been discovered by scientists.

The researchers at Weill Cornell Medical College explained that faulty wiring occurs when RNA molecules embedded in a growing axon are not degraded after they give instructions that help steer the nerve cell. So, for example, the signal that tells the axon to turn-which should disappear after the turn is made-remains active, interfering with new signals meant to guide the axon in other directions.

The scientists said that there might be a way to use this new knowledge to fix the circuits.

"Understanding the basis of brain miswiring can help scientists come up with new therapies and strategies to correct the problem," said the study's senior author, Dr. Samie Jaffrey, a professor in the Department of Pharmacology.

"The brain is quite 'plastic' and changeable in the very young, and if we know why circuits are miswired, it may be possible to correct those pathways, allowing the brain to build new, functional wiring," he said.

Disorders associated with faulty neuronal circuits include epilepsy, autism, schizophrenia, mental retardation and spasticity and movement disorders, among others.

In this study, researchers investigated neurons that travel up the spinal cord into the brain.

"It is very critical that axons are precisely positioned in the spinal cord. If they are improperly positioned, they will form the wrong connections, which can lead to signals being sent to the wrong target cells in the brain," Dr. Jaffrey said.

The team found that RNA molecules embedded in the growth cone are responsible for instructing the axon to move left or right, up or down. These RNAs are translated in growth cones to produce antenna-like proteins that steer the axon like a self-guided missile.

"As a circuit is being built, RNAs in the neuron's growth cones are mostly silent. We found that specific RNAs are only read at precise stages in order to produce the right protein needed to steer the axon at the right time. After the protein is produced, we saw that the RNA instruction is degraded and disappears," he said.

"If these RNAs do not disappear when they should, the axon does not position itself properly-it may go right instead of left-and the wiring will be incorrect and the circuit may be faulty," Dr. Jaffrey explained.

The research finding answers a long-standing puzzle in the quest to understand brain wiring, added Dr. Dilek Colak, a postdoctoral associate in Dr. Jaffrey's laboratory.

The study was published in the journal Cell.

Source: ANI