, Volume 49, Issue 5, pp 316–326 | Cite as

Effects of Aging and Noise Exposure on Auditory Brainstem Responses and Number of Presynaptic Ribbons in Inner Hair Cells of C57BL/6J Mice

  • Sh. Takeda
  • P. Mannström
  • S. Dash-Wagh
  • T. Yoshida
  • M. Ulfendahl

C57BL/6J mice develop age-related hearing loss (HL) early in life. The influence of aging and noise exposure on the number of presynaptic structures in inner hair cells of C57BL/6J mice has not been studied. We monitored auditory brainstem responses, ABRs, in C57BL/6J mice over time and assessed changes in the number of inner hair cell presynaptic ribbons. Multifaceted verification of the effects of aging and noise exposure on hearing in the C57BL/6J strain was performed. The HL was additively increased by noise exposure in 5-week-old mice. The earliest change observed was a decrease in the amplitude of the ABR first wave. Hair cells and spiral ganglion neurons were also lost. Immunohistochemistry and high-resolution confocal microscopy revealed decreased numbers of CtBP2-positive structures in the inner hair cells localized in other than those in the low-frequency region of the cochlea. On the other hand, the influence of acute noise exposure on the inner hair cell ribbons was observed only within the highest-frequency area.


auditory brainstem response C57 cochlear synaptopathy CtBP2 hearing loss inner hair cell ribbons 


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  1. 1.
    B. Yueh, N. Shapiro, C. H. MacLean, and P. G. Shekelle, “Screening and management of adult hearing loss in primary care: scientific review,” J. Am. Med. Assoc. 289, 1976-1985 (2003).CrossRefGoogle Scholar
  2. 2.
    F. R. Lin, R. Thorpe, S. Gordon-Salant, and L. Ferrucci, “Hearing loss prevalence and risk factors among older adults in the United States,” J. Gerontol. Biol. Sci. Med. Sci., 66, 582-590 (2011).CrossRefGoogle Scholar
  3. 3.
    S. G. Kujawa and M. C. Liberman, “Acceleration of agerelated hearing loss by early noise exposure: evidence of a misspent youth,” J. Neurosci. 26, 2115-2123 (2006).CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    E. Daniel, “Noise and hearing loss: a review,” J. School Health, 77, No. 5, 225-231 (2007).CrossRefPubMedGoogle Scholar
  5. 5.
    D. O. Mikaelian, “Development and degeneration of hearing in the C57/b16 mouse: relation of electrophysiologic responses from the round window and cochlear nucleus to cochlear anatomy and behavioral responses,” Laryngoscope, 89, 1-15 (1979).CrossRefPubMedGoogle Scholar
  6. 6.
    K. R. Henry and R. A. Chole, “Genotypic differences in behavioral, physiological and anatomical expressions of age-related hearing loss in the laboratory mouse,” Audiology, 19, 369-383 (1980).CrossRefPubMedGoogle Scholar
  7. 7.
    J. F. Willott, J. Kulig, and T. Satterfield, “The acoustic startle response in DBA/2 and C57BL/6 mice: relationship to auditory neuronal response properties and hearing impairment,” Hear. Res., 16, 161-167 (1984).CrossRefPubMedGoogle Scholar
  8. 8.
    J. F. Willott, “Effects of aging, hearing loss, and anatomical location on thresholds of inferior colliculus neurons in C57BL/6 and CBA mice,” J. Neurophysiol., 56, 391-408 (1986).CrossRefPubMedGoogle Scholar
  9. 9.
    K. Parham and J. F. Willott, “Acoustic startle response in young and aging C57BL/6J and CBA/J mice,” Behav. Neurosci., 102, 881 (1988).CrossRefPubMedGoogle Scholar
  10. 10.
    V. P. Spongr, D. G. Flood, R. D. Frisina, and R. J. Salvi, “Quantitative measures of hair cell loss in CBA and C57BL/6 mice throughout their life spans,” J. Acoust. Soc. Am., 101, 3546-3553 (1997).CrossRefPubMedGoogle Scholar
  11. 11.
    R. R. Davis, J. K. Newlander, X. B. Ling, et al., “Genetic basis for susceptibility to noise-induced hearing loss in mice,” Hear. Res., 155, 82-90 (2001).CrossRefPubMedGoogle Scholar
  12. 12.
    J. F. Willott, J. G. Turner, S. Carlson, et al., “The BALB/c mouse as an animal model for progressive sensorineural hearing loss,” Hear. Res., 115, 162-174 (1998).CrossRefPubMedGoogle Scholar
  13. 13.
    L. C. Erway, J. F. Willott, J. R. Archer, and D. E. Harrison, “Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains,” Hear. Res., 65, 125-132 (1993).CrossRefPubMedGoogle Scholar
  14. 14.
    K. Noben-Trauth, Q. Y. Zheng, and K. R. Johnson, “Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss,” Natl. Genet., 35, 21-23 (2003).CrossRefGoogle Scholar
  15. 15.
    J. Siemens, C. Lillo, R. A. Dumont, et al., “Cadherin 23 is a component of the tip link in hair-cell stereocilia,” Nature, 428, 950-955 (2004).CrossRefPubMedGoogle Scholar
  16. 16.
    S. P. Zachary and P. A. Fuchs, “Re-emergent inhibition of cochlear inner hair cells in a mouse model of hearing loss,” J. Neurosci., 35, No. 26, 9701-9706 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    H. F. Schuknecht, The Pathology of the Ear, Harvard Univ. Press, Cambridge (1974).Google Scholar
  18. 18.
    H. S. Li and E. Borg, “Age-related loss of auditory sensitivity in two mouse genotypes,” Acta Otolaryngol., 111, 827-834 (1991).CrossRefPubMedGoogle Scholar
  19. 19.
    S. Hequembourg and M. C. Liberman, “Spiral ligament pathology: a major aspect of age-related cochlear degeneration in C57BL/6 mice,” J. Assoc. Res. Otolaryngol., 2, 118-129 (2001).CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    M. C. Liberman, “Morphological differences among radial afferent fibers in the cat cochlea: an electronmicroscopic study of serial sections,” Hear. Res., 3, 45-63 (1980).CrossRefPubMedGoogle Scholar
  21. 21.
    Y. Sergeyenko, K. Lall, M. C. Liberman, and S. G. Kujawa, “Age-related cochlear synaptopathy: an earlyonset contributor to auditory functional decline,” J. Neurosci., 33, 13686-13694 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    A. C. Furman, S. G. Kujawa, and M. C. Liberman, “Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates,” J. Neurophysiol., 110, 577-586 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    D. L. Newman, L. M. Fisher, J. Ohmen, et al., “GRM7 association with age-related hearing loss and its extension to additional features of presbycusis,” Hear. Res., 294, 125-132 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    S. F. Maison, H. Usubuchi, and M. C. Liberman., “Efferent feedback minimizes cochlear neuropathy from moderate noise exposure,” J. Neurosci., 33, 5542-5552 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    S. Stamataki, H. W. Francis, M. Lehar, et al., “Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice,” Hear. Res., 221, 104-118 (2006).CrossRefPubMedGoogle Scholar
  26. 26.
    H. J. G. Gundersen, “The nucleator,” J. Microscop., 151, 3-21 (1988).CrossRefGoogle Scholar
  27. 27.
    A. Møller, P. Strange, and H. J. G. Gundersen, “Efficient estimation of cell volume and number using the nucleator and the disector,” J. Microscop., 159, 61-71 (1990).CrossRefGoogle Scholar
  28. 28.
    T. Tandrup, “A method for unbiased and efficient estimation of number and mean volume of specified neuron subtypes in rat dorsal root ganglion,” J. Comp. Neurol., 329, 269-276 (1993).CrossRefPubMedGoogle Scholar
  29. 29.
    F. Watanabe, M. Kirkegaard, S. Matsumoto, et al., “Signaling through erbB receptors is a critical functional regulator in the mature cochlea,” Eur. J. Neurosci., 32, 717-724 (2010).CrossRefPubMedGoogle Scholar
  30. 30.
    P. Mannström, B. Ulfhake, M. Kirkegaard, and M. Ulfendahl, “Dietary restriction reduces age-related degeneration of stria vascularis in the inner ear of the rat,” Exp. Gerontol., 48, 1173-1179 (2013).CrossRefPubMedGoogle Scholar
  31. 31.
    H. J. G. Gundersen, T. F. Bendtsen, L. Korbo, et al., “Some new, simple and efficient stereological methods and their use in pathological research and diagnosis,” Apmis, 96, 379-394 (1988).CrossRefPubMedGoogle Scholar
  32. 32.
    H. J. G. Gundersen, P. Bagger, T. F. Bendtsen, et al., “The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis,” Apmis, 96, 857-881 (1988).CrossRefPubMedGoogle Scholar
  33. 33.
    H. C. Ou, G. W. Harding, and B. A. Bohne, “An anatomically based frequency–place map for the mouse cochlea,” Hear. Res., 145, 123-129 (2000).CrossRefPubMedGoogle Scholar
  34. 34.
    A. Viberg and B. Canlon, “The guide to plotting a cochleogram,” Hear. Res., 197, 1-10 (2004).CrossRefPubMedGoogle Scholar
  35. 35.
    J. F. Willott, J. VandenBosche, T. Shimizu, et al., “Effects of exposing C57BL/6J mice to high-and lowfrequency augmented acoustic environments: Auditory brainstem response thresholds, cytocochleograms, anterior cochlear nucleus morphology and the role of gonadal hormones,” Hear. Res., 235, 60-71 (2008).CrossRefPubMedGoogle Scholar
  36. 36.
    R. D. Frisina and X. Zhu, “Auditory sensitivity and the outer hair cell system in the CBA mouse model of agerelated hearing loss,” Open Access Anim. Physiol., 2, 9-16 (2010).CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    J. S. Buchwald and C. H. Huang, “Far-field acoustic response: origins in the cat,” Science, 189, 382-384 (1975).CrossRefPubMedGoogle Scholar
  38. 38.
    S. G. Kujawa and M. C. Liberman, “Synaptopathy in the noise-exposed and aging cochlea: primary neural degeneration in acquired sensorineural hearing loss,” Hear. Res., 330, 191-199 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    I. Tasaki, “The electrosaltatory transmission of the nerve impulse and the effect of narcosis upon the nerve fiber,” Am. J. Physiol., 127, 211-227 (1939).Google Scholar
  40. 40.
    N. Y. Kiang, M. C. Liberman, and R. A. Levine, “Auditory-nerve activity in cats exposed to ototoxic drugs and high-intensity sounds,” Ann. Otol. Rhinol. Laryngol., 85, 752-768 (1976).CrossRefPubMedGoogle Scholar
  41. 41.
    H. Spoendlin, “Factors inducing retrograde degeneration of the cochlear nerve,” Ann. Otol. Rhinol. Laryngol., Suppl., 112, 76-82 (1983).Google Scholar
  42. 42.
    G. M. Cohen, J. C. Park, and J. S. Grasso, “Comparison of demyelination and neural degeneration in spiral and Scarpa’s ganglia of C57BL/6 mice,” J. Electron Microscop. Tech., 15, 165-172 (1990).CrossRefGoogle Scholar
  43. 43.
    T. Kurioka, M. Y. Lee, A. N. Heeringa, et al., “Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus,” Neuroscience, 332, 242-257 (2016).CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    H. Spoendlin, “Innervation patterns in the organ of Corti of the cat,” Acta Otolaryngol., 67, 239-254 (1969).CrossRefPubMedGoogle Scholar
  45. 45.
    D. Robertson, “Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea,” Hear. Res., 9, 263-278 (1983).CrossRefPubMedGoogle Scholar
  46. 46.
    M. C. Liberman and N. Y. Kiang, “Acoustic trauma in cats: cochlear pathology and auditory-nerve activity,” Acta Otolaryngol., 358, 1-63 (1978).Google Scholar
  47. 47.
    A. M. Taberner and M. C. Liberman, “Response properties of single auditory nerve fibers in the mouse,” J. Neurophysiol., 93, 557-569 (2005).CrossRefPubMedGoogle Scholar
  48. 48.
    R. A. Schmiedt, J. H. Mills, and F. A. Boettcher, “Agerelated loss of activity of auditory-nerve fibers,” J. Neurophysiol., 76, 2799-2803 (1996).CrossRefPubMedGoogle Scholar
  49. 49.
    S. G. Kujawa and M. C. Liberman, “Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss,” J. Neurosci., 29, 14077-14085 (2009).CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    J. Bourien, Y. Tang, C. Batrel, et al., “Contribution of auditory nerve fibers to compound action potential of the auditory nerve,” J. Neurophysiol., 112, No. 5, 1025-1039 (2014).CrossRefPubMedGoogle Scholar
  51. 51.
    H. W. Lin, A. C. Furman, S. G. Kujawa, and M. C. Liberman, “Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift,” J. Assoc. Res. Otolaryngol., 12, 605-616 (2011).CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    K. K. Ohlemiller, J. M. Lett, and P. M. Gagnon, “Cellular correlates of age-related endocochlear potential reduction in a mouse model,” Hear. Res., 220, 10-26 (2006).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sh. Takeda
    • 1
    • 2
    • 3
  • P. Mannström
    • 1
  • S. Dash-Wagh
    • 1
  • T. Yoshida
    • 2
  • M. Ulfendahl
    • 1
  1. 1.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Department of OtolaryngologyEhime University Graduate School of MedicineMatsuyamaJapan
  3. 3.Oiki Ear and Nose SurgicenterOsakaJapan

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