SHAFAQNA – Noise-induced hearing loss is associated with damaged synapses that connect the nerves and hair cells in the cochlea – a part of the inner ear. But a new mouse study suggests noise-induced hearing loss can be prevented with a simple chemical compound that protects the nerves that stimulate the cochlea .The researchers, from Weill Cornell Medical College in New York, NY, report their findings in the journal Cell Metabolism.
They explain that the cochlea transmits sound messages through nerves to the spiral ganglion, which, in turn, passes those messages to the brain. When an individual is exposed to loud noises, the synapses connecting the cochlear nerves and hair cells become damaged, resulting in hearing loss.
Dr. Kevin Brown, lead author and associate professor at the University of North Carolina School of Medicine (he conducted the research while at Weill Cornell), says that one of the “major limitations in managing disorders of the inner ear, including hearing loss, is there are a very limited number of treatment options.”
To explore potential treatments, he and his team used the chemical nicotinamide riboside (NR) – a precursor to vitamin B3 – on mice before or after exposing them to loud noises.
From this, the researchers observed that NR successfully prevented damage to the synaptic connections in the mice, preventing both long- and short-term hearing loss.
Additionally, the team found that NR was equally effective when given both before or after the mice were exposed to the noise.
‘NR gets into cells and can be absorbed orally’
In previous work, Dr. Brown and colleagues had shown that nicotinamide adenine dinucleotide (NAD+) – to which NR is a precursor – protected cochlea nerve cells from being injured. However, because NAD+ is unstable, the researchers were unsure of whether it could be used in a live animal.
As such, they decided to use NR, which is a stable compound. Dr. Samie Jaffrey, co-senior author from Weill Cornell, explains:
“NR gets into cells very readily and can be absorbed when you take it orally. It has all the properties that you would expect in a medicine that could be administered to people.”
Though the results of their latest study have important implications for avoiding hearing loss, the researchers say they could be applied to the treatment of age-related conditions, such as pulmonary hypertension.
The key lies in the protein sirtuin 3 (SIRT3), which is involved in the function of the powerhouses of the cell, the mitochondria. Through their research, the team showed that NR and NAD+ prevent hearing loss by increasing the activity of SIRT3.
From this finding, the team theorized that enhancement of SIRT3 is linked to the protective properties of NR.
Findings could help in treatment for metabolic syndromes
To further investigate, the researchers tweaked SIRT3 levels independently of NR in order to observe whether they could still prevent hearing loss due to noise exposure by dispensing NR.
They found that deleting the SIRT3 gene in the mice cancelled any protective properties of NR. Additionally, the researchers demonstrated that a new strain of mice that were engineered to express high levels of SIRT3 were naturally resistant to noise-induced hearing loss, even in the absence of NR.
Because SIRT3 decreases as we age, the researchers say this could explain age-related hearing loss. And some individuals have different versions of the SIRT 3 genes that reduce enzyme activity, making them more susceptible to noise-induced hearing loss.
Commenting on their research, Dr. Eric Verdin, study author and professor of medicine at the University of California-San Francisco, says:
“The success of this study suggests that targeting SIRT3 using NR could be a viable target for treating all sorts of aging-related disorders – not only hearing loss, but also metabolic syndromes like obesity, pulmonary hypertension, and even diabetes.”