Don't shout, I'm not deaf!

"Chemical headphones" will help to avoid hearing loss

Polina Gershberg, Naked Science

A group of biologists from the University of Iowa and Washington University in St. Louis has identified a receptor whose blocking will help to avoid deterioration and complete hearing loss. An article about this is published in the Proceedings of the National Academy of Sciences (Hu et al., Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca ²⁺-permeable AMPA receptors).

The inner hair cells of the cochlea (green and blue) excite the auditory nerve fibers (red), releasing the neurotransmitter glutamate, which helps convert sound waves into electrical signals entering the brain. Figure from the press release of Washington University School of Medicine in St. Louis Noise-induced hearing loss blocked with drug compound – VM.

The researchers studied hair cells that are responsible for the mechanical amplification of sound vibrations (external hair cells) and the transformation of these vibrations into neural impulses (internal cells). Scientists have found that there is no GluA2 protein on the receptors of some cells involved directly in the transmission of a signal to neurons. It is the functioning of such receptors that underlies the hearing disorder called selective deafness, or cochlear synaptopathy.

Glutamate plays an important role in synaptic transmission of audio signals. However, too loud sounds or constant noise of moderate volume causes hair cells to secrete excessive amounts of glutamate, which disrupts the normal functioning of synaptic contacts.

The release of glutamate stimulates the receptors of cells devoid of GluA2, and a stream of calcium ions begins to flow into these cells. Once inside, the ions trigger a number of pathological mechanisms, which leads to cell death. Previously, scientists assumed that the cells in these synapses are impervious to calcium ions.

Experiments on mice have shown that blocking such defective receptors prevents the development of synaptopathy under the influence of excessive noise loads. To do this, biologists used an adamantane derivative called IEM-1460.

Chemical structure of IEM-1460 / Cayman Chemical. The researchers themselves compared this approach with the use of "chemical headphones" that block destructive processes occurring in synapses between hair cells and neurons.

"These headphones prevent damage from loud sounds, but do not completely drown out the sound," says one of the authors of the study, Stephen Green, professor of biology. "By blocking GluA2-deficient receptors, aka calcium-permeable receptors, damage [to cells] can be prevented, and the mouse can hear very well because it still has GluA2-containing receptors mediating synaptic signal transmission."

A similar drug can be used to prevent synaptopathy in humans. Such a tool could be useful to artillery soldiers who constantly hear very loud volleys. Interestingly, the study was partially funded by the US Department of Defense.

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