Putting the Hex on Fragile X

24 May 2007 (All day)

Meredith et al./VU University Amsterdam

Weak link.
Improving the signalling capacity of prefrontal cortex cells like this one could be the key to overcoming Fragile X syndrome.

A stimulating environment can undo the physiological effects of mental retardation in laboratory mice, researchers have found. The discovery might pave the way toward similar therapy for children afflicted with a similar kind of retardation called Fragile X syndrome, although the parallels with the human condition aren't perfect.

Fragile X is one of the most common causes of mental retardation, generated by the inheritance of a defective gene called fmr1. Affecting about one in 4000 people, its manifestations include diminished abilities to learn and memorize, as well as anxiety in the presence of strangers and an overall stressful disposition. In the new experiments, researchers from VU University in Amsterdam, the Netherlands, used lab mice containing the deactivated fmr1 gene. These mice also have learning deficiencies.

First, the scientists set out to identify the underlying neurological defect in the mice. To do so, they analyzed mouse nerve cells from the prefrontal cortex--an important part of the brain for learning and memory. These cells showed a diminished capacity to store information for more than a few minutes, a trait known in normal individuals as long-term potentiation. They found that the defect lengthens a part of neurons called the dendritic spine, which makes it more difficult for the cells to transfer calcium ions, a critical ability for maintaining strong electrochemical signals between neurons.

After 2 months, they detected long-term potentiation in the prefrontal cortex cells. In other words, although Fragile X syndrome tends to inhibit brain cells from storing information, the research shows that exposing Fragile X mice to stimulating environments improves the communication between the nerve cells, says neuroscientist and co-author Huib Mansvelder. He says the new findings, reported in today's issue of the journal Neuron, "provide strong scientific support" to investigate in Fragile X patients "what the best way would be to challenge these patients and stimulate brain activity." He adds that the approach might even benefit victims of other forms of learning deficiencies as well.

Cell biologist William Greenough of the University of Illinois in Urbana-Champaign remains somewhat skeptical. Although he thinks the study provides a "plausible mechanism" for overcoming the effects of Fragile X syndrome in mice, "when it comes to enriching the environment in a human home, I think many parents have tried to provide stimulation and the effects have been much less dramatic," he says.

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