title: Adenosine receptors regulate susceptibility to noise-induced neural injury in the mouse cochlea and hearing loss.
abstract: Our previous studies have shown that the stimulation of A1adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A1AR and A2AAR null mice (A1AR-/-and A2AAR-/-). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A1AR-/-mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceeded the hearing loss in the WT and A2AAR-/-mice. All mice experienced the loss of OHC, synaptic ribbons and SGN after noise exposure, but the loss of SGN was significantly higher in A1AR-/-mice than in the A2AAR-/-and WT genotypes. The A2AAR-/-demonstrated better preservation of OHC and afferent synapses and the minimal loss of SGN after noise exposure. The findings suggest that the loss of A1AR expression results in an increased susceptibility to cochlear neural injury and hearing loss, whilst absence of A2AAR increases cochlear resistance to acoustic trauma.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand. Electronic address: s.vlajkovic@auckland.ac.nz.
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Vlajkovic
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand.
authors.forename: Kaushi
authors.initials: K
authors.lastname: Ambepitiya
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand.
authors.forename: Meagan
authors.initials: M
authors.lastname: Barclay
authors.affiliation: RS Dow Neurobiology Laboratories, Legacy Research, Portland, OR, 97232, USA.
authors.forename: Detlev
authors.initials: D
authors.lastname: Boison
authors.affiliation: Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand; Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D003051:Cochlea / Q000293:injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D020022:Genetic Predisposition to Disease; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000473:pathology; D006309:Hearing; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009622:Noise / Q000009:adverse effects*; D010641:Phenotype; D065840:Protective Factors; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D013136:Spiral Ganglion / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A
keywords: Adenosine receptors; Cochlea; Hearing loss; Noise; Spiral ganglion neurons; Synaptic ribbons