Old mice lacking high-affinity nicotine receptors resist acoustic trauma.

There is presently no clearly effective preventative medication against noise-induced hearing loss (NIHL). However, negative feedback systems that presumably evolved to modulate the sensitivity of the organ of Corti may incidentally confer protection. One feedback system implicated in protection from NIHL involves synaptic connections between the lateral olivocochlear efferent terminals and the afferent fibers of spiral ganglion neurons (SGNs). These connections operate via high-affinity nicotinic acetylcholine receptors containing the β2 subunit. We unexpectedly observed protection from NIHL in 9-month old knockout mice lacking the β2 subunit (β2(-/-)); however, the same protection was not observed in 2-month old β2(-/-) mice. This enigmatic observation led to the discovery that protection from acoustic trauma in older β2(-/-) mice is mainly mediated by an age-related increase of corticosterone, not disruption of efferent cholinergic transmission. Significant protection of inner hair cells after acoustic trauma in β2(-/-) mice was linked to the activation of glucocorticoid signaling pathways. However, significant loss of SGNs was observed in animals with chronically high systemic levels of corticosterone. These results suggested a "double-edge sword" nature of glucocorticoid signaling in neuronal protection, and a need for caution regarding when to apply synthetic glucocorticoid drugs to treat neural injury such as accompanies acoustic trauma.