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Biological Chemistry

Brain Self-Soothes With Inhibitory Protein

Researchers identify elusive molecule, diazepam binding inhibitor, which behaves like the antianxiety drug valium and regulates the brain’s electrical activity

by Lauren K. Wolf
June 3, 2013 | A version of this story appeared in Volume 91, Issue 22

Ever since scientists learned in the 1970s that the anxiety medication Valium calms the brain by binding to specific protein receptors there, they’ve suspected the cognitive organ of making its own Valium-like compound to regulate nerve cell activity. More than 30 years later, John R. Huguenard of Stanford University School of Medicine and colleagues have pinpointed the naturally synthesized molecule (Neuron 2013, DOI: 10.1016/j.neuron.2013.04.026). Dubbed diazepam binding inhibitor (DBI), the small protein—or a peptide fragment thereof—sticks to the same receptor on nerve cells as does Valium, sending a signal to quiet the brain. The team confirmed that DBI causes Valium-like effects by measuring electrical activity in the neurons of mice engineered to lack the gene for DBI. These rodents had a higher risk of strong epileptic seizures than did normal mice. When the researchers added DBI back to a region of the brain called the thalamus, the mice became less prone to seizure. “Our brains are all capable of normal function and, with the wrong electrical stimulus, of seizures,” Huguenard says. The team thinks that when electrical activity in the brain’s thalamus gets too intense, nerve cells in that region secrete DBI to calm the ruckus and keep things working evenly.


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