https://doi.org/10.4081/ejh.2023.3748
Expression and localization of α2A-adrenergic receptor in the rat post-natal developing cochlea
Submitted: 11 April 2023
Accepted: 22 July 2023
Published: 7 August 2023
Accepted: 22 July 2023
Abstract Views: 430
PDF: 371
Supplementary: 45
HTML: 6
Supplementary: 45
HTML: 6
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Lots of adrenergic receptors (ARs) are widely present across the auditory pathways and are positioned to affect auditory and vestibular functions. However, noradrenergic regulation in the cochlea has not been well characterized. In this study, a rat model of noise-induced hearing loss was developed to investigate the expression of α2A-adrenergic receptor (AR) after acoustic trauma, then, we investigated the expression of α2A-AR in the developing rat cochlea using immunofluorescence, qRT-PCR, and Western blotting. We found that the expression of α2A-AR significantly increased in rats exposed to noise compared with controls. Immunofluorescence analysis demonstrated that α2A-AR is localized on hair cells (HCs), spiral ganglion neurons (SGNs), and the stria vascularis (SV) in the postnatal developing cochlea from post-natal day (P) 0 to P28. Furthermore, we observed α2A-AR mRNA reached a maximum level at P14 and P28 when compared with P0, while no significant differences in α2A-AR protein levels at the various stages when compared with P0. This study provides direct evidence for the expression of α2A-AR in HCs, SGNs, and the SV of the cochlea, indicating that norepinephrine might play a vital role in hearing function within the cochlea through α2A-AR.
Nagaraj BS, Linthicum FH Jr. Autonomic innervation of the human middle ear: an immunohistochemical study. Am J Otolaryngol 1998;19:75-82.
DOI: https://doi.org/10.1016/S0196-0709(98)90099-0
Uddman R, Kitajiri M, Sundler F. Autonomic innervation of the middle ear. Ann Otol Rhinol Laryngol 1983;92:151-4.
DOI: https://doi.org/10.1177/000348948309200211
Hozawa K, Kimura RS. Cholinergic and noradrenergic nervous systems in the cynomolgus monkey cochlea. Acta Otolaryngol 1990;110:46-55.
DOI: https://doi.org/10.3109/00016489009122514
Borg E, Densert O, Flock A. Synaptic vesicles in the cochlea. Acta Otolaryngol 1974;78:321-32.
DOI: https://doi.org/10.3109/00016487409126362
Spoendlin H, Lichtensteiger W. The adrenergic innervation of the labyrinth. Acta Otolaryngol 1966;61:423-34.
DOI: https://doi.org/10.3109/00016486609127080
Densert O, Flock A. An electron-microscopic study of adrenergic innervation in the cochlea. Acta Otolaryngol 1974;77:185-97.
DOI: https://doi.org/10.3109/00016487409124616
Kuo SP, Trussell LO. Spontaneous spiking and synaptic depression underlie noradrenergic control of feed-forward inhibition. Neuron 2011;71:306-18.
DOI: https://doi.org/10.1016/j.neuron.2011.05.039
Hirao K, Eto K, Nakahata Y, Ishibashi H, Nagai T, Nabekura J. Noradrenergic refinement of glutamatergic neuronal circuits in the lateral superior olivary nucleus before hearing onset. J Neurophysiol 2015;114:1974-86.
DOI: https://doi.org/10.1152/jn.00813.2014
Tebecis AK. Effects of monoamines and amino acids on medial geniculate neurones of the cat. Neuropharmacology 1970;9:381-90.
DOI: https://doi.org/10.1016/0028-3908(70)90035-3
Torda C. Effects of noradrenaline and serotonin on activity of single lateral and medial geniculate neurons. Gen Pharmacol 1978;9:455-62.
DOI: https://doi.org/10.1016/0306-3623(78)90035-6
Edeline JM, Manunta Y, Hennevin E. Induction of selective plasticity in the frequency tuning of auditory cortex and auditory thalamus neurons by locus coeruleus stimulation. Hear Res 2011;274:75-84.
DOI: https://doi.org/10.1016/j.heares.2010.08.005
Manunta Y, Edeline JM. Effects of noradrenaline on frequency tuning of rat auditory cortex neurons. Eur J Neurosci 1997;9:833-47.
DOI: https://doi.org/10.1111/j.1460-9568.1997.tb01433.x
Manunta Y, Edeline JM. Effects of noradrenaline on frequency tuning of auditory cortex neurons during wakefulness and slow-wave sleep. Eur J Neurosci 1999;11:2134-50.
DOI: https://doi.org/10.1046/j.1460-9568.1999.00633.x
Martins AR, Froemke RC. Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex. Nat Neurosci 2015;18:1483-92.
DOI: https://doi.org/10.1038/nn.4090
Arima J, Kubo C, Ishibashi H, Akaike N. alpha2-Adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones. J Physiol 1998;508:57-66.
DOI: https://doi.org/10.1111/j.1469-7793.1998.057br.x
Kirkwood A, Rozas C, Kirkwood J, Perez F, Bear MF. Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. J Neurosci 1999;19:1599-609.
DOI: https://doi.org/10.1523/JNEUROSCI.19-05-01599.1999
Qu Y, Eysel UT, Vandesande F, Arckens L. Effect of partial sensory deprivation on monoaminergic neuromodulators in striate cortex of adult cat. Neuroscience 2000;101:863-8.
DOI: https://doi.org/10.1016/S0306-4522(00)00441-3
Ishibashi H, Umezu M, Jang IS, Ito Y, Akaike N. Alpha 1-adrenoceptor-activated cation currents in neurones acutely isolated from rat cardiac parasympathetic ganglia. J Physiol 2003;548:111-20.
DOI: https://doi.org/10.1113/jphysiol.2002.033100
Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006;80:53-83.
DOI: https://doi.org/10.1016/j.pneurobio.2006.08.001
Devilbiss DM, Page ME, Waterhouse BD. Locus ceruleus regulates sensory encoding by neurons and networks in waking animals. J Neurosci 2006;26:9860-72.
DOI: https://doi.org/10.1523/JNEUROSCI.1776-06.2006
Sternini C. Organization of the peripheral nervous system: autonomic and sensory ganglia. J Investig Dermatol Symp Proc 1997;2:1-7.
DOI: https://doi.org/10.1038/jidsymp.1997.2
Hein L. Adrenoceptors and signal transduction in neurons. Cell Tissue Res 2006;326:541-51.
DOI: https://doi.org/10.1007/s00441-006-0285-2
Zhang Z, Chai R. Hear the sounds: the role of G protein-coupled receptors in the cochlea. Am J Physiol Cell Physiol 2022;323:C1088-C99.
DOI: https://doi.org/10.1152/ajpcell.00453.2021
Ma X, Guo J, Fu Y, Shen C, Jiang P, Zhang Y, et al. G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss. Front Mol Neurosci 2022;15:1028125.
DOI: https://doi.org/10.3389/fnmol.2022.1028125
Khan KM, Drescher MJ, Hatfield JS, Ramakrishnan NA, Drescher DG. Immunohistochemical localization of adrenergic receptors in the rat organ of corti and spiral ganglion. J Neurosci Res 2007;85:3000-12.
DOI: https://doi.org/10.1002/jnr.21404
Gruber DD, Dang H, Shimozono M, Scofield MA, Wangemann P. Alpha1A-adrenergic receptors mediate vasoconstriction of the isolated spiral modiolar artery in vitro. Hear res 1998;119:113-24.
DOI: https://doi.org/10.1016/S0378-5955(98)00036-7
Cai J, Li J, Liu W, Han Y, Wang H. alpha2-adrenergic receptors in spiral ganglion neurons may mediate protective effects of brimonidine and yohimbine against glutamate and hydrogen peroxide toxicity. Neuroscience 2013;228:23-35.
DOI: https://doi.org/10.1016/j.neuroscience.2012.10.004
Cai J, Li J, Mao Y, Bai X, Xu L, Wang H. Immunohistochemical localization of alpha2-adrenergic receptors in the neonatal rat cochlea and the vestibular labyrinth. J Mol Neurosci 2013;51:1010-20.
DOI: https://doi.org/10.1007/s12031-013-0089-2
Carrasco VN, Prazma J, Faber JE, Triana RJ, Pillsbury HC. Cochlear microcirculation. Effect of adrenergic agonists on arteriole diameter. Arch Otolaryngol Head Neck Surg 1990;116:411-7.
DOI: https://doi.org/10.1001/archotol.1990.01870040033009
Zha DJ, Wang ZM, Lin Y, Liu T, Qiao L, Lu LJ, et al. Effects of noradrenaline on the GABA response in rat isolated spiral ganglion neurons in culture. J Neurochem 2007;103:57-66.
DOI: https://doi.org/10.1111/j.1471-4159.2007.04776.x
Martin F, Marianowski R, Tu TY, Herman P, Tran Ba Huy P. Modulation of cyclic AMP production by strial marginal cells from gerbil in culture. Hear Res 1994;81:33-41.
DOI: https://doi.org/10.1016/0378-5955(94)90150-3
Ishii K, Zhai WG, Akita M. Effect of a beta-stimulant on the inner ear stria vascularis. Ann Otol Rhinol Laryngol 2000;109:628-33.
DOI: https://doi.org/10.1177/000348940010900703
Schicknick H, Henschke JU, Budinger E, Ohl FW, Gundelfinger ED, Tischmeyer W. beta-adrenergic modulation of discrimination learning and memory in the auditory cortex. Eur J Neurosci 2019;50:3141-63.
DOI: https://doi.org/10.1111/ejn.14480
Fauser C, Schimanski S, Wangemann P. Localization of beta1-adrenergic receptors in the cochlea and the vestibular labyrinth. J Membr Biol 2004;201:25-32.
DOI: https://doi.org/10.1007/s00232-004-0703-x
Kim BG, Kim JY, Jung J, Moon IS, Yoon JH, Choi JY, et al. beta1- and beta2-adrenergic stimulation-induced electrogenic transport by human endolymphatic sac epithelium and its clinical implications. Sci Rep 2017;7:42217.
Schimanski S, Scofield MA, Wangemann P. Functional beta2-adrenergic receptors are present in nonstrial tissues of the lateral wall in the gerbil cochlea. Audiol Neurootol 2001;6:124-31.
DOI: https://doi.org/10.1159/000046819
de Minteguiaga C, Clerget MS, Tran Ba Huy P, Elalouf JM. beta2-adrenergic but not vasopressin V2 receptor mRNAs are expressed in the stria vascularis of the rat inner ear. Pflugers Arch 1998;436:940-7.
DOI: https://doi.org/10.1007/s004240050727
Wada T, Takahashi K, Ito Z, Hara A, Takahashi H, Kasakari J. The protective effect of the sympathetic nervous system against acoustic trauma. Auris Nasus Larynx 1999;26:375-82.
DOI: https://doi.org/10.1016/S0385-8146(99)00017-6
Hildesheimer M, Sharon R, Muchnik C, Sahartov E, Rubinstein M. The effect of bilateral sympathectomy on noise induced temporary threshold shift. Hear Res 1991;51:49-53.
DOI: https://doi.org/10.1016/0378-5955(91)90006-U
Horner KC, Giraudet F, Lucciano M, Cazals Y. Sympathectomy improves the ear's resistance to acoustic trauma--could stress render the ear more sensitive? Eur J Neurosci 2001;13:405-8.
DOI: https://doi.org/10.1046/j.0953-816X.2000.01386.x
Giraudet F, Horner KC, Cazals Y. Similar half-octave TTS protection of the cochlea by xylazine/ketamine or sympathectomy. Hear Res 2002;174:239-48.
DOI: https://doi.org/10.1016/S0378-5955(02)00698-6
Hildesheimer M, Henkin Y, Pye A, Heled S, Sahartov E, Shabtai EL, et al. Bilateral superior cervical sympathectomy and noise-induced, permanent threshold shift in guinea pigs. Hear Res 2002;163:46-52.
DOI: https://doi.org/10.1016/S0378-5955(01)00371-9
Maison SF, Le M, Larsen E, Lee SK, Rosowski JJ, Thomas SA, et al. Mice lacking adrenergic signaling have normal cochlear responses and normal resistance to acoustic injury but enhanced susceptibility to middle-ear infection. J Assoc Res Otolaryngol 2010;11:449-61.
DOI: https://doi.org/10.1007/s10162-010-0220-9
Yu B, Zhang G, An Y, Wang W. Morroniside on anti-inflammation activities in rats following acute myocardial infarction. Korean J Physiol Pharmacol 2018;22:17-21.
DOI: https://doi.org/10.4196/kjpp.2018.22.1.17
Wang P, Zhang P, Huang J, Li M, Chen X. Trichostatin A protects against cisplatin-induced ototoxicity by regulating expression of genes related to apoptosis and synaptic function. Neurotoxicology 2013;37:51-62.
DOI: https://doi.org/10.1016/j.neuro.2013.03.007
Matsubara A, Miyashita T, Inamoto R, Mori N. Presence of adrenergic receptors in rat endolymphatic sac epithelial cells. J Membr Biol 2013;246:109-14.
DOI: https://doi.org/10.1007/s00232-012-9508-5
Lee G, Park H, Park HS, Lee JG. Modulation of alpha 1 adrenergic receptors on urinary bladder in rat spinal cord injury model. Int Neurourol J 2012;16:62-8.
DOI: https://doi.org/10.5213/inj.2012.16.2.62
Lamm K, Zajic G, Schacht J. Living isolated cells from inner ear vessels: a new approach for studying the regulation of cochlear microcirculation and vascular permeability. Hear Res 1994;81:83-90.
DOI: https://doi.org/10.1016/0378-5955(94)90155-4
Schuknecht HF, Gacek MR. Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol 1993;102:1-16.
DOI: https://doi.org/10.1177/00034894931020S101
Ohlemiller KK. Age-related hearing loss: the status of Schuknecht's typology. Curr Opin Otolaryngol Head Neck Surg 2004;12:439-43.
DOI: https://doi.org/10.1097/01.moo.0000134450.99615.22
Spoendlin H, Lichtensteiger W. The sympathetic nerve supply to the inner ear. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 1967;189:346-59.
DOI: https://doi.org/10.1007/BF00440938
Spoendlin H. Autonomic innervation of the inner ear. Adv Otorhinolaryngol 1981;27:1-13.
DOI: https://doi.org/10.1159/000400324
Perlman HB, Kimura R, Fernandez C. Experiments on temporary obstruction of the internal auditory artery. Laryngoscope 1959;69:591-613.
DOI: https://doi.org/10.1288/00005537-195906000-00001
Thalmann R, Miyoshi T, Thalmann I. The influence of ischemia upon the energy reserves of inner ear tissues. Laryngoscope 1972;82:2249-72.
DOI: https://doi.org/10.1288/00005537-197212000-00013
Santi PA, Duvall AJ, 3rd. Stria vascularis pathology and recovery following noise exposure. Otolaryngology 1978;86:ORL354-61.
DOI: https://doi.org/10.1177/019459987808600229
Ren T, Brown NJ, Zhang M, Nuttall AL, Miller JM. A reversible ischemia model in gerbil cochlea. Hear Res 1995;92:30-7.
DOI: https://doi.org/10.1016/0378-5955(95)00192-1
Lamm K, Arnold W. Noise-induced cochlear hypoxia is intensity dependent, correlates with hearing loss and precedes reduction of cochlear blood flow. Audiol Neurootol 1996;1:148-60.
DOI: https://doi.org/10.1159/000259195
Nuttall AL. Sound-induced cochlear ischemia/hypoxia as a mechanism of hearing loss. Noise Health 1999;2:17-32.
Mom T, Bonfils P, Gilain L, Avan P. Origin of cubic difference tones generated by high-intensity stimuli: effect of ischemia and auditory fatigue on the gerbil cochlea. J Acoust Soc Am 2001;110:1477-88.
DOI: https://doi.org/10.1121/1.1390337
Shi X. Physiopathology of the cochlear microcirculation. Hear Res 2011;282:10-24.
DOI: https://doi.org/10.1016/j.heares.2011.08.006
Kim BG, Kim JY, Jung J, Moon IS, Yoon JH, Choi JY, et al. beta(1)- and beta(2)-adrenergic stimulation-induced electrogenic transport by human endolymphatic sac epithelium and its clinical implications. Sci Rep 2017;7:42217.
DOI: https://doi.org/10.1038/srep42217
Ohlsen KA, Baldwin DL, Nuttall AL, Miller JM. Influence of topically applied adrenergic agents on cochlear blood flow. Circ Res 1991;69:509-18.
DOI: https://doi.org/10.1161/01.RES.69.2.509
Liu SY, Pitovski DZ, Shivapuja BG. Alpha 1-adrenergic receptors in the mammalian cochlea. Acta Otolaryngol 1996;116:710-3.
DOI: https://doi.org/10.3109/00016489609137911
Drescher MJ, Drescher DG, Khan KM, Hatfield JS, Ramakrishnan NA, Abu-Hamdan MD, et al. Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea. Neuroscience 2006;142:139-64.
DOI: https://doi.org/10.1016/j.neuroscience.2006.05.065
Cortada M, Levano S, Bodmer D. Brimonidine protects auditory hair cells from in vitro-induced toxicity of gentamicin. Audiol Neurootol 2017;22:125-34.
DOI: https://doi.org/10.1159/000479218
Wangemann P, Liu J, Shimozono M, Schimanski S, Scofield MA. K+ secretion in strial marginal cells is stimulated via beta 1-adrenergic receptors but not via beta 2-adrenergic or vasopressin receptors. J Membr Biol 2000;175:191-202.
DOI: https://doi.org/10.1007/s00232001067
Inamoto R, Miyashita T, Matsubara A, Hoshikawa H, Mori N. The difference in endolymphatic hydrostatic pressure elevation induced by isoproterenol between the ampulla and the cochlea. Auris Nasus Larynx 2017;44:282-7.
DOI: https://doi.org/10.1016/j.anl.2016.07.018
Ethics Approval
All animal procedures were conducted in compliance with the National Research Council's Guide for the Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Committee of the Air Force Medical University, Xi’an, Shannxi Province, China.Supporting Agencies
National Natural Science Foundation of China , National Key Research and Development Plan , Natural Science Foundation of Shaanxi , Shaanxi Provincial Clinical Medical Research Center , Research Promotion project from Xijing HospitalHow to Cite
Tian, C., Yang, Y., Li, Y., Sun, F., Qu, J., & Zha, D. (2023). Expression and localization of α<sub>2A</sub>-adrenergic receptor in the rat post-natal developing cochlea. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3748
Copyright (c) 2023 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
