Public release date: 19-Sep-2013 [ | E-mail | Share ]

Contact: Sarah Smith sas2072@med.cornell.edu 646-317-7401 Weill Cornell Medical College

NEW YORK (September 19, 2013) -- Researchers at Weill Cornell Medical College have discovered why a tiny alteration in a brain gene, found in 20 percent of the population, contributes to the risk for anxiety, depression and memory loss.

Their discovery, reported in Nature Communications, describes new functions for the alteration, a single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene. This gene is a powerful regulator of the growth and function of neurons, and the establishment of brain circuitry. The common alteration occurs when a single "letter" of BDNF's genetic code is "misspelled."

The team of investigators, led by Dr. Clay Bracken, associate research professor of biochemistry and director of the nuclear magnetic resonance facility, Dr. Barbara Hempstead, professor of medicine, and Dr. Francis Lee, professor of psychiatry, all at Weill Cornell Medical College, discovered that the alteration appears to induce shrinkage of neurons from the hippocampus (an important region for memory and emotion), reducing connectivity between brain cells.

The discovery upends the prevailing theory about how the BDNF SNP alters the function of the brain, says Dr. Agustin Anastasia, first author of the article and a postdoctoral fellow in the Hempstead lab. "Research on BDNF is very active worldwide, and the conventional wisdom of the field was that the SNP reduced the amount of BDNF that was secreted. Therefore, many investigators were trying to increase production of the protein -- but this effort was only moderately successful."

"While the SNP does decrease the amount of BDNF in neurons, it generates a protein, the Met66 prodomain, that is different from the Val66 prodomain that is generated by the 80 percent of the human population that does not carry the SNP," Dr. Hempstead says. "The Met66 prodomain binds to specific proteins on the surface of neurons, to induce the pruning or shrinkage of these neurons."

The findings offer mechanistic insight into why some depression and anxiety runs in families, Dr. Lee says. "There can be a heritable component to these diseases and it makes sense that a common variant in a gene could be involved," he says. "Just like hypertension contributes to the risk for heart disease, the BDNF alteration increases the risk of depression, anxiety and memory disorders -- but is not the sole reason why they occur."

Still, targeted treatment for the genetic alteration could provide the first true benefit for affected patients, who often don't respond to traditional treatments, Dr. Lee says. "We can easily test patients for the mutation by using a simple blood test," he says. "We just need novel targeted treatments that alter the effects of the BDNF SNP-- and now we have a good lead on what that therapy should do."

The other half of the story

Read more here:
Researchers tease apart workings of a common gene

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