Journal Club

Highlighting recently published papers selected by Academy members

Can flies at a rock concert hear the next day?

When the crowd filters out of the concert hall at the end of a loud, live rock concert, each person’s ears have paid a toll. Whether a concert-goer hears a ringing, speaks a little louder in the car ride home, or doesn’t notice symptoms until they’ve attended years of rock concerts, the sound-sensing hair cells in their ears have been irreparably damaged to some degree. The same damage occurs in the ears of soldiers exposed to a nearby blast, or laborers that work day-in-day-out in a loud factory. But does the same thing happen to animals exposed to loud noises? To make progress in developing a laboratory model of so-called acoustic trauma, researchers analyzed the effects of rock-concert-level noises on the fly Drosophila melanogaster. The flies, they reported this week in a PNAS Early Edition paper, experience molecular changes to their sound-sensing cells that mimic those seen in humans.

The new observations provide a path forward to study the cellular pathways and processes involved in acoustic trauma, and potentially develop ways to prevent or reverse the ultimate death of the ear cells exposed to loud noises.

“The basic outcomes of noise trauma are understood in terms of hair cell dying,” says senior author Daniel F. Eberl of the University of Iowa. “But there are questions about the basic pathways that are activated or suppressed, as well as the issue of chronic exposure to noise.”

Studying acoustic trauma in humans relies on retrospective studies linking past sound exposure to current hearing abilities. It can be “tricky to inconclusively associate these,” Eberl says, or to home in on molecules involved in the initial responses of the ear to loud noise. Animal models offer a way to perform prospective and controlled studies. His team chose to focus on Drosophila because compared to other model organisms used in the lab to study hearing, such as mice and guinea pigs, flies are easier to manipulate genetically and have shorter generation times. So they’re ideal for pinning down the roles of particular molecules in physiological processes—genes can be knocked out and the effects measured. And although the overall structure of flies’ hearing organs differs somewhat from that in humans, the developmental origins and the molecules involved are largely conserved.

Eberl’s team exposed two different strains of Drosophila to loud noise and then measured—over the following week—changes to the flies’ hearing abilities, physiology, and behavior.

“The noise level that we exposed the flies to, for 24 hours, was in the range of a loud rock concert or a constant jackhammer,” says Eberl. “These are levels that would have very significant effects in mammals.”

Immediately after the noise exposure, the flies had delayed reactions to brief noises, a measure of hearing loss. And the flies’ behaviors also changed—whereas male flies usually respond to the sound of female songs with displays of courtship, they no longer reacted to these songs after the traumatic noise exposure. When the researchers looked at the ear hair cells of the flies, they also found changes at the cellular level.

Seven days after the initial acoustic trauma, overall hearing ability had returned to normal, but mitochondria—energy generating organelles—inside the ear hair cells had shrunk. Small mitochondria are an overall sign of cellular stress, Ebert says, and often the first step toward the initiation of cellular suicide pathways. And mitochondrial shrinkage has been shown to be a step in the response of humans’ ear hair cells after loud noise exposure as well. The observation in flies suggested that similar pathways were at play in humans and flies after noise exposure.

To illustrate the usefulness of the fly as a model for understanding how certain genes and proteins are involved the molecular effects of acoustic trauma, Ebert’s lab next repeated the experiments in flies with a mutation in the nervana 3 gene, known to be expressed in the neurons of the fly’s auditory system. These flies had hearing abilities identical to the controls before traumatic noise exposure. But afterward, effects on the mitochondria appeared even faster—within 24 hours—and diminished hearing lasted for the full seven days of follow-up observation.

Next, Ebert says, the researchers would like to repeat the experiments in other strains of flies, study the effects of repeated noise exposure rather than one-time acoustic trauma, and search out additional genes and proteins that are potentially involved by using genome-wide gene expression studies to pinpoint pathways that are altered in ear cells after noise exposure.

“The idea is to give us an idea of pathways that we can potentially manipulate with chemical compounds,” he says. “What if there were a pill that you could take before you go to a rock concert that would make your hair cells insensitive to this exposure?”

Categories: Neuroscience
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