title: Mice lacking adrenergic signaling have normal cochlear responses and normal resistance to acoustic injury but enhanced susceptibility to middle-ear infection.
abstract: The vasculature and neurons of the inner ear receive adrenergic innervation from the cervical sympathetic chain, and adrenergic receptors may be expressed by cells of the organ of Corti and stria vascularis, despite a lack of direct sympathetic innervation. To assess the functional role of adrenergic signaling in the auditory periphery, we studied mice with targeted deletion of the gene for dopamine beta-hydroxylase (DBH), which catalyzes the conversion of dopamine to noradrenaline; thus, these mutant mice have no measurable adrenaline or noradrenaline. Dbh (-/-) mice were more susceptible to spontaneous middle-ear infection than their control littermates, consistent with a role for sympathetics in systemic and/or local immune response. At 6-8 weeks of age, cochlear thresholds and suprathreshold responses assessed by auditory brainstem responses and distortion product otoacoustic emissions, as well as light-microscopic morphology, were indistinguishable from controls, if ears with conductive hearing loss were eliminated. Dbh (-/-) mice were no more susceptible to acoustic injury than controls, despite prior reports that sympathectomy reduces noise damage. Dbh (-/-) mice showed enhancement of shock-evoked olivocochlear suppression of cochlear responses, which may arise from the loss of adrenergic inputs to olivocochlear neurons in the brainstem. However, adrenergic modulation of olivocochlear efferents does not mediate the protective effect of contralateral cochlear destruction on ipsilateral response to acoustic overexposure.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA. stephane_maison@meei.harvard.edu
authors.forename: Stéphane F
authors.initials: SF
authors.lastname: Maison
authors.forename: Mina
authors.initials: M
authors.lastname: Le
authors.forename: Erik
authors.initials: E
authors.lastname: Larsen
authors.forename: Suh-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: John J
authors.initials: JJ
authors.lastname: Rosowski
authors.forename: Steven A
authors.initials: SA
authors.lastname: Thomas
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000818:Animals; D003051:Cochlea / Q000294:innervation / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010033:Otitis Media / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*
chemical_list: D011941:Receptors, Adrenergic; D004299:Dopamine beta-Hydroxylase