October 2011 – AHRF-funded researchers Qiong Wang, PhD, and Steven Green, PhD, both at the University of Iowa, have found that damage caused by exposure to loud noises in the inner ear may occur long before changes in hearing are perceived. They have also identified a chemical factor that may aid in restoring hearing loss due to noise exposure. Their findings were published in the May 25, 2011 issue of The Journal of Neuroscience.
The researchers studied intact cochlear cultures consisting of hair cells and spiral ganglion neurons (SGNs) taken from mice. Hair cells are structures within the cochlea that pick up sound and translate it into signals carried by auditory nerves (the SGNs) to the brain, where the signals are interpreted as sound.
Exposure to very loud noise can kill the hair cells and cause hearing loss, a phenomenon that has been well known for many decades. Much more recent research has revealed another, even more insidious consequence of noise. Noise levels too low to kill hair cells are still able to cause irreversible damage to the cochlea, damage that may not be immediately evident but that results in accelerated hearing loss over the following decades of life. This is a particular problem in young people exposed to moderately high noise, such as constantly listening to mp3 players at high volume, or attending loud concerts. Damage included a loss of connection between the hair cells and their SGNs. Loss of contact between hair cells and some SGNs may not have much impact on hearing and people affected may not experience any hearing loss at the time of the incident, but the hidden damage—loss of some hair cells-SGN connections— is still there. Over time, the loss of contact with hair cells causes SGNs to die leading to faster or more severe hearing loss with aging or subsequent exposure to noise.
“Most people who think they have normal hearing are probably living with some level of hearing damage- they just don’t notice it,” says Wang. “Just being exposed to some of the sounds of everyday life, over time, can have an effect on the inner ear, especially loud or prolonged exposure to noise.”
The question tackled by Wang and Green was how to develop an in vitro (outside a living organism) system to study noise damage to hair cell-SGN connections. With the help of novel experimental techniques, Wang and Green were able to culture intact cochlear tissue from rats and mice consisting of hair cells, their associated SGNs, and preserve the connections between them. They exposed the tissue to high levels of glutamate, a substance released in excess from hair cells during acoustic trauma and observed damage to the hair cell-SGN connections very much like that observed after noise in living animals.
Next, Wang and Green applied two neurotrophic factors to the tissue- neurotrophin-3 (NT-3), which is known to be crucial for normal development of the cochlea during embryonic development, and BDNF, another neurotrophic factor involved in cochlear development. “NT-3 is actually produced by the hair cells and is necessary for maintaining the connection between SGNs and hair cells,” says Wang.
They found that both these factors stimulated formation of connections and regrowth of the SGNs in their culture tissue after mimicking noise exposure using glutamate. They also found that NT-3 has a unique role that can’t be substituted by application of BDNF.
The researchers believe that when the SGNs retract, they lose contact with hair cells and their normal supply of NT-3. They may be permanently lost if the supply isn’t reestablished quickly enough. Addition of NT-3 encouraged reconnection and could be a promising component of future therapies.
“Exposure to lots of loud noise when you are young does lead to accelerated age-related hearing loss later in life,” Wang says, “indicating that the damage from noise early in life continues to have deleterious effects over time.” She believes this may be due to lost connections between hair cells and SGNs that never recover.
The research helps shed light on the complex chemical communication between hair cells and SGNs and hints as to how it may be harnessed for therapeutic interventions to treat acoustic trauma in the future. Dr. Green adds that “it is a long road from these initial observations to therapy and the best advice for now is to turn down the volume when using earbuds!”