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Valium-like Proteins Made in the Brain May Lead to Better Treatment for Epilepsy, Anxiety and Sleep Disorders

May 31, 2013 01:03 PM EDT

Proteins secreted only in the brain may act as a Valium-like brake on certain types of epileptic seizures, according to a new study led by scientists at Stanford University School of Medicine.

The protein, known as diazepam binding inhibitor (DBI), calms the rhythms of a key brain circuit and thus could prove valuable in developing new therapies with fewer side effects not only for epilepsy but possibly anxiety and sleep disorders as well, according to researchers.

"This is one of the most exciting findings we have had in many years," John Huguenard, professor of neurology and neurological sciences and the study's senior author, said in a press release. "Our results show for the first time that a nucleus deep in the middle of the brain generates a small protein product, or peptide, that acts just like benzodiazepines."

For years, scientists have known DBI but under the name ACBP, and is found in every cell in the body. However, it wasn't until the recent study, published in the journal Neuron, that scientists were aware of its particular role in the brain.

"In this circuit, DBI or one of its peptide fragments acts just like Valium biochemically and produces the same neurological effect," Huguenard said.

The way it works, the authors said, is DBI binds to receptors that sit on nerve-cell surfaces and are responsive to the small but key neurotransmitter GABA.

This chemical messenger then binds to receptors on nearby nerve cells, rendering them temporarily unable to fire electrical signals.
Benzodiazepine drugs work by enhancing GABA-induced inhibition by binding to a different site on GABA receptors than the one GABA binds to, making it hyper-responsive to the neurotransmitter. DBI, too, works by binding to the same spot benzodiazepines bind.

However, until now, the result of this phenomenon has not been clear.

Together, the Stanford team zeroed in on DBI’s function in the thalamus, the relay station for sensory information, based on previous studies conducted in Huguenard’s lab that indicated the deep-brain structure is implicated in the onset of seizures.

In so doing, they were able to demonstrate that DBI is capable of the same inhibition-boosting effect on benzodiazepine-responsive GABA receptors as benzodiazepines themselves.

Furthermore, the researchers were able to show that this was as true on nerve cells in an adjacent thalamic region even though no DBI is naturally generated in or it.

Ultimately, the scientists found, the actions of DBI on GABA receptors appear to be tightly controlled in order to occur in very specific areas in the brain.

At this point, the scientists are not sure whether it is DBI or one of its peptide fragments actually performing the inhibitory role; however, Huguenard said, by finding out exactly which cells are releasing DBI under what biochemical circumstances, it may be possible one day to develop agents that could start and boost its ability to nip seizures in the bud.

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