INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Alpha9Alpha10 nicotinic cholinergic receptors and protection from acoustic trauma
Autor/es:
ELGOYHEN AB
Lugar:
Chicago, USA
Reunión:
Simposio; Nicotinic Acetylcholine Receptors as Therapeutic Targets: Frontiers in Basic Research & Clinical Science, Satellite Symposium to the 39th Annual Meeting, Society for Neuroscience; 2009
Resumen:
The Medial Olivocochlear System and Protection from Acoustic Trauma Ana Belén Elgoyhen, Institute for Research in Genetic Engineering and Molecular Biology, CONICET, Buenos Aires, Argentina, elgoyhen@dna.uba.ar Sound-induced acoustic injury is one of the most common causes of hearing loss and tinnitus. Although prevention from exposure to intense sound would be the obvious way to keep our inner ear healthy, finding alternatives to increase resistance to damage is a research field of great interest. The medial olivocochlear (MOC) pathway provides inhibitory feedback, through the release of acetylcholine (ACh) from brainstem neurons onto outer hair cells (OHCs) of the cochlea, reducing their ability to amplify sounds, and thus reducing cochlear sensitivity. Although many possible roles for this pathway have been proposed, understanding remains incomplete. We have explored the MOC pathway’s function by generating a strain of genetically modified mice carrying a mutation in the nicotinic acetylcholine receptor (nAChR) subunit expressed by OHCs. We tested the effect of the mutation by recording signals from hair cells in cochlear preparations in vitro. Mutant hair cells exhibited greater sensitivity to exogenous ACh and the synaptic currents were prolonged in comparison to wild type preparations, indicating that the mutation enhanced nAChR function. To determine the consequences of this enhanced receptor function for cochlear responses, we measured auditory brainstem responses and distortion product otoacoustic emissions. The threshold levels of sound required to evoke these responses were elevated in the mutant mice, suggesting that the baseline inhibitory effect of the MOC pathway was enhanced. Furthermore, suppression of OHC-mediated amplification produced by stimulating the MOC pathway electrically was enhanced and dramatically prolonged in mutant mice. Surprisingly, mutant mice had a greater resistance to permanent acoustic injury resulting from exposure to 100 dB sounds, indicating that activation of the MOC feedback can protect the inner ear from noise-induced damage. Thus, the efferent pathway provides a promising target for pharmacological prevention of inner ear pathologies derived from acoustic injury, such as hearing loss and tinnitus. Finding drugs that mimic the effect of the mutation would be the developmental path to follow.