Background

Hearing loss as a result of exposure to loud noise is a significant problem. The problem is also likely to increase in the future as our work and social environments become increasingly noisy. However, exposure to a low level of sound prior to exposure to damaging levels of sound can offer protection. This phenomenon is called "sound conditioning" but the mechanisms underlying this phenomenon are poorly understood.

Aim

Professor Canlon's research group investigated sound conditioning at the molecular and cellular level. They also explored the effects of sound conditioning after noise trauma.

Benefit

The identification of molecules and biological processes associated with noise-induced hearing loss is the first step towards developing treatments to reduce hearing loss caused by loud noise.

Achievements

Protection against noise-induced hearing loss by sound conditioning after noise exposure

The group showed that sound conditioning can also reduce the adverse effects of loud noise if the sound conditioning is delivered immediately after the damaging noise.

Molecular and Cellular processes associated with sound and stress conditioning

Neurotransmitter systems

As well as sending signals to the brain, the cochlea also receives signals from the auditory processing parts of the brain. This 'feedback' is thought to be involved in protecting the sensory hair cells during loud noise. Professor Canlon's team have studied one of these feedback pathways (lateral efferent system) and a specific neurotransmitter (dopamine) used by the neurons in this system. Their results show that damaging levels of sound cause a reduction in the amount of tyrosine hydroxylase (an enzyme involved in the synthesis of dopamine) and in two of the receptors that bind dopamine. In contrast, low-level noise that protects hearing results in an increase in tyrosine hydroxylase and the dopamine receptors. Therefore, their results suggest that dopaminergic activity within the lateral efferent system is involved in protecting hearing.

Programmed cell death

Exposure to loud noise can cause the sensory hair cells of the cochlea to die, contributing to hearing loss. The process by which these cells die is called apoptosis and is tightly controlled. After noise trauma, apoptosis is triggered by the release of cytochrome c into the cytosol of the cell. The Karolinska group has shown that sound conditioning increases the amount of a protein called bcl2 in sensory hair cells. This protein functions to suppress the release of cytochrome c, so stops the cell from dying.

Stress-induced hormone changes

Corticosterone is a major glucocorticoid hormone released in response to stress. It binds to glucocorticoid receptors triggering a response in the target cell. The research group at the Karolinska institute investigated whether or not this hormonal response to stress can protect against the damaging effects of noise. First they showed that sound conditioning as well as systemic stress protected animals from noise-induced hearing loss. They then used drugs to block the release of corticosterone and the activation of the glucocorticoid receptors, and repeated the experiments. The results showed that the protective effects associated with the conditioning procedures were lost, suggesting that the glucocortcoid hormone system is involved in mediating the protective effects.

Molecular and cellular changes associated with age-related hearing loss

Professor Canlon's laboratory also studied a specific strain of mouse that suffers from age-related hearing loss. Hair cells and neurons are lost with increasing age in these mice and the group correlated these peripheral changes with changes in the central auditory system of the brain, in particular the cochlear nucleus. They confirmed that there was an age-related decline in the number of neurons and also observed an up regulation in the levels of certain calcium binding proteins within the cochlear nucleus.

Impact