Biologists identify hearing-loss receptor, use drug to prevent hearing damage
Once we start to lose our hearing, we can’t get it back. And if we ignore hearing loss, we run the risk of permanent cognitive damage, including dementia. But scientists now believe they can prevent hearing loss by blocking the effects of loud noises.
Biologists at the University of Iowa and Washington University in St Louis have identified a receptor that, when blocked, can prevent a common type of hearing loss.
Receptors are part of a suite of molecules on nerve cells in the ear that bridge the passage of sound and auditory information from inner-ear hair cells – the sound sensors – to the brain. The successful transmission of sound from hair cells to nerve cells, which occurs through a junction called a synapse, is integral to hearing in animals, including humans.
The researchers found that some receptors involved in the hair cell-to-nerve cell transmission lack a protein called GluA2, and it is these receptors that are responsible for synaptopathy, or hearing loss caused by irreparable damage to the synapses.
The biologists used a drug in mice to selectively block the GluA2-lacking receptors, and prevent the mice from experiencing synaptopathy when exposed to noise.
They likened their approach to fitting the mice with chemical earmuffs. The earmuffs effectively prevented the mice from sustaining hearing damage by blocking the breakdown that occurs in some synapses between inner ear hair cells and nerve cells as a result of loud noises.
“It wasn't just putting earmuffs on – these earmuffs prevent the damage caused by loud sounds but don't muffle the sound,” said Steven Green, professor in the department of biology and corresponding author on the study.
The experiments in mice indicate there is the potential to inject a drug that would prevent hearing damage in people before they are exposed to damaging noise, such as soldiers who encounter loud sounds in their duties.
“Permanent hearing damage can be caused by noise levels that have been considered ‘safe’ and people need to be careful about noise exposure because we can't yet repair synapses or regenerate hair cells,” Prof. Green said. “Our chemical earmuffs are, currently, an indication of the direction research can go, not yet a proven, safe means of protection in humans.”
In hearing, a chemical called glutamate is released from hair cells. This chemical transmits sound information at the synapse between inner-ear hair cells and nerve cells. However, loud sounds or even sustained moderate noise – such as sound coming through earbuds – cause the hair cells to release a glut of glutamate, effectively gumming the synaptic transmission of sound to brain neurons.
Specifically, it is the entry of calcium into the inner ear neurons through GluA2-lacking glutamate receptors that leads to synaptopathy.
The researchers identified at the molecular-level receptors without GluA2, meaning those terminals that could cause hearing damage by allowing a flow of calcium.
Even more, they then learnt that if they blocked the receptors without GluA2, the GluA2-containing receptors picked up the slack, and hearing was maintained.
In the mice experiments, they showed a drug called IEM-1460 could target – and block – the receptors without GluA2.
“What we found is if you block the GluA2-lacking receptors, a.k.a. calcium-permeable receptors, then you can prevent the damage, and the mouse can hear just fine because it still has the GluA2-containing receptors that can mediate synaptic transmission,” Prof. Green said.
“Now, we have a drug that doesn't prevent hearing, but does prevent hearing damage.”
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