Fragile X syndrome is the most commonly inherited form of mental retardation. It appears to transform some brain cells into chatterboxes, say scientists at Washington University School of Medicine in St. Louis.
All this extra chatter makes it more difficult for brain cells to identify and respond to the important signals. This leads to attention problems, similar to those found in autism. In fact, thirty percent of fragile X patients are autistic.
Symptoms of fragile X include mental retardation, hyperactivity, epilepsy, impulsive behavior, and delays in speech and walking. The disorder also affects anatomy, leading to unusually large heads, flat feet, large body size and distinctive facial features.
“We don’t know precisely how information is encoded in the brain, but we presume that some signals are important and some are noise,” says senior author Vitaly Klyachko, PhD, assistant professor of cell biology and physiology.
“Our theoretical model suggests that the changes we detected may make it much more difficult for brain cells to distinguish the important signals from the noise.”
Fragile X is caused by mutations in a gene called Fmr1. This gene is found on the X chromosome, one of the two sex chromosomes. Females have two copies of that chromosome, while males have only one. Because of this, fragile X syndrome is more common in males, and the effects in males tend to be more severe.
Scientists deleted the Fmr1 gene several years ago in mice to create a model of fragile X. Without this gene, the mice showed social and behavioral deficits similar to those seen in human fragile X.
Normally, brain signals travel as surges of electrical energy. These surges only last for tiny fractions of a second. This action causes a brief release of neurotransmitters into the short gap between nerve cells.
“The axons are putting out much more neurotransmitter than they should, and we think this confuses the system and overloads the circuitry,” Klyachko explains. “It may also create problems in terms of brain cells using up their resources much more quickly than they normally would.”
When the researchers injected a synthetic copy of the gene (called FMRP) into the brain cells of the mouse models, it quickly restored the electrical surges to a normal length.
The researchers are continuing to study FMRP. They hope to learn more about how information is encoded and processed at the level of individual brain cells. According to the researchers, understanding the effects of this faulty signaling will be important in developing successful treatments for fragile X and autism.
The research is published in the journal Neuron.