Lack of proteins too cause epilepsy, deafness

Washington, Jan 25: A study in mice conducted by scientists at the University of California, San Francisco has provided a pathway for exploring the hereditary causes of deafness and epilepsy in humans.

In the study, the researchers found that mice genetically engineered to lack a particular protein in the brain had profound deafness and seizures. They said that more broadly, the finding provides an entry point for gaining new insight into the role of glutamate, the chemical messenger carried by the protein.

The absent protein is a particular 'vesicular neurotransmitter transporter,' a machine within nerve cells that ferries chemical messengers, or 'neurotransmitters,' from the fluid-filled cytoplasm into vesicles that are positioned at the tips of nerve cells and serve to release neurotransmitters onto neighbouring cells.

Transporters and neurotransmitters work as a team to make all neural communication in the brain possible. While the neurotransmitter glutamate is the major excitatory messenger in the brain, the neurotransmitter GABA is the major inhibitory messenger, sending signals that reduce excitation and anxiety.

Two other neurotransmitters, dopamine and serotonin, modulate the activity of neural circuits to influence mood, sleep and other aspects of behaviour.

Scientists are already aware of two vesicular glutamate transporters, VGLUT1 and VGLUT2, which are expressed on nerve cells that release glutamate.

Recently, the researchers identified VGLUT3, which is expressed primarily by nerve cells that release GABA, serotonin and acetylcholine, another neurotransmitter.

VGLUT3 is also released in some non-nerve cells, in tissues outside the brain. With these findings, the researchers suspected that VGLUT3 might support some function other than neurotransmission.

In the study, the researchers investigated the role of VGLUT3 in mice genetically engineered to lack the transporter. The found the effect to be dramatic.

"Mice lacking the transporter are completely deaf from birth. Moreover, they had significant seizures," said the senior author of the study, Robert Edwards, MD, professor of neurology and physiology at University of California, San Francisco.

According to the researchers, as the gene that encodes VGLUT3 is known to have sequence variations in humans, it is possible that these or other variations may be the underlying cause of deafness or epilepsy in humans.

ANI