Study identifies the genetic cause and mechanism for noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is becoming increasingly prevalent. Urban crowding means that large cities are getting noisier, particularly in developing countries. WHO predicts that by 2030, one billion people will be at risk of noise-induced hearing loss.  Some of us have less effective natural defenses against the impact of overexposure to sound than others.  Five million people in France end up suffering from hearing loss, which has a negative impact on their social life.

Hearing aids are one solution, however, they work by exposing the wearer to amplified sounds with researchers working hard to find syndromic and genetic causes for NIHL.  Now, researchers led by the  Institut Pasteur state they have identified the molecule, known as  pejvakin, responsible for noise-induced hearing loss, one of the most common causes of deafness. The team state that their findings offer new prospects for the treatment of this condition.  The opensource study is published in the journal Cell.

Earlier studies from the team identified a new gene that was responsible for early-onset sensorineural hearing loss. Audiometric tests performed on individuals with mutations in this gene subsequently revealed an unusually high level of diversity in hearing impairments, in terms of both severity and characteristics. The current study clarifies the reasons for this heterogeneity and shows that the gene codes for the protein pejvakin.

The current study used young mice whose pejvakin gene had been inactivated. Results show an astonishing variation in hearing impairments from one mouse to the next, ranging from mild to profound hearing loss. The lab explain that young mice are highly vocal for the first three weeks after they are born, particularly when feeding; the more mice in a cage, the noisier their acoustic environment. Data findings show that as the number of mice in the cage increased, so did their hearing threshold, that is, the minimum sound level at which they are able to hear sounds. The group state that by using direct, controlled acoustic stimulation, they were able to prove that the auditory system of mice lacking in pejvakin is affected by their acoustic environment.

The researchers then set about investigating the physiological causes of this phenomenon. They observed that in mice without pejvakin, the auditory sensory cells are damaged as soon as they are exposed to even seemingly harmless sounds, the equivalent of a minute spent in a nightclub for humans. Results show that these cells need two weeks of silence to become functional again, and with prolonged or repeated exposure, the cells eventually die. Data findings also show that the noise-sensitive element in the cell as being the peroxisome, a small organelle involved in detoxification.

Results from human studies show that the auditory sensory cells in people with impaired pejvakin were extremely vulnerable to noise. When a standard hearing test was performed on these hearing-impaired individuals, the responses of their auditory sensory cells and neurons, although normal to begin with, gradually worsened as the test went on as a result of the sounds used.  The lab conclude that they have identified a genetic form of NIHL, by showing that pejvakin deficiency in mice and DFNB59 patients leads to hypervulnerability to sound, due to a peroxisomal deficiency. To their knowledge, a peroxisomal cause of an isolated (non-syndromic) form of inherited deafness has not been reported yet.

The team surmise that they don’t yet know what percentage of the population is either lacking in pejvakin or has a less effective form of the protein. They go on to add that their findings indicate that in these people, hearing aids are most probably not only ineffective but also harmful.  For the future, the researchers will now look into possible techniques to restore the function of pejvakin, particularly using gene therapy, which has already proved successful in conserving hearing in mice lacking in pejvakin, even when they are overexposed to noise.

Source: Institut Pasteur

Sound exposure induces a proliferation of peroxisomes (in green) in the auditory sensory cells of mice harboring pejvakin (Pjvk+/+, center) and causes their degeneration in mice lacking pejvakin (Pjvk-/-, right). Credit: Institut Pasteur.

Sound exposure induces a proliferation of peroxisomes (in green) in the auditory sensory cells of mice harboring pejvakin (Pjvk+/+, center) and causes their degeneration in mice lacking pejvakin (Pjvk-/-, right).
Credit: Institut Pasteur.

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