Skip to main content

Advertisement

SpringerLink
Log in

Activity-Dependent Neurodegeneration and Neuroplasticity of Auditory Neurons Following Conductive Hearing Loss in Adult Mice

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

We examined the functional and structural changes of auditory neurons (ANs) in adult mice after conductive hearing loss (CHL). Earplugs (EPs) were bilaterally inserted in male 8-week-old mice for 4 weeks [EP(+) group] and subsequently removed for 4 weeks [EP(+/−) group]. We examined the control mice [EP(−) group] with no EPs inserted at 12 weeks. The auditory brainstem response (ABR) was measured to determine the cochlear function before and after EP insertion, after EP removal, and at 4 weeks following EP removal. We examined the cochleae for hair cell (HC) and spiral ganglion neuron survival, synaptic and neural properties, and AN myelination. There was a significant elevation of the ABR threshold across all tested frequencies after EP insertion. After removing the occlusion, these threshold shifts were fully recovered. Compared with the EP(−) mice, the EP(+) mice showed a significant decrease in the ABR peak 1 amplitude and a significantly prolonged latency at all tested frequencies. There was no significant effect of auditory deprivation on the survival of HCs and ANs. Conversely, auditory deprivation caused significant damage to the synapses and myelin and a significant decrease in the AN size. Although functional changes in the ABR amplitude and latency did not fully recover in the EP(+/−) mice, almost all anatomical changes were fully recovered in the EP(+/−) mice; however, cochlear synapses only showed partial recovery. These results suggest that auditory activities are required to maintain peripheral auditory synapses and myelination in adults. The auditory deprivation model allows for assessment of the mechanisms of synaptopathy and demyelination in the auditory periphery, and synaptic and myelin regeneration in sensorineural hearing loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aizawa N, Eggermont JJ (2007) Mild noise-induced hearing loss at young age affects temporal modulation transfer functions in adult cat primary auditory cortex. Hear Res 223:71–82

    Article  Google Scholar 

  • Barclay M, Constable R, James NR, Thorne PR, Montgomery JM (2016) Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea. Neuroscience 325:50–62

    Article  CAS  Google Scholar 

  • Chomiak T, Hu B (2009) What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach. PLoS ONE 4:e7754

    Article  Google Scholar 

  • Clarkson C, Antunes FM, Rubio ME (2016) Conductive hearing loss has long-lasting structural and molecular effects on presynaptic and postsynaptic structures of auditory nerve synapses in the cochlear nucleus. J Neurosci 36:10214–10227

    Article  CAS  Google Scholar 

  • Fujimoto C, Yamasoba T (2019) Mitochondria-targeted antioxidants for treatment of hearing loss: a systematic review. Antioxidants 8(4):109

    Article  CAS  Google Scholar 

  • Kim KX, Payne S, Yang-Hood A, Li SZ, Davis B, Carlquist JBVG, Gantz JA, Kallogjeri D, Fitzpatrick JAJ, Ohlemiller KK, Hirose K, Rutherford MA (2019) Vesicular glutamatergic transmission in noise-induced loss and repair of cochlear ribbon synapses. J Neurosci 39:4434–4447

    Article  Google Scholar 

  • Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. J Neurosci 29:14077–14085

    Article  CAS  Google Scholar 

  • Kujawa SG, Liberman MC (2015) Synaptopathy in the noise-exposed and aging cochlea: primary neural degeneration in acquired sensorineural hearing loss. Hear Res 330:191–199

    Article  Google Scholar 

  • Kurioka T, Matsunobu T, Satoh Y, Niwa K, Endo S, Fujioka M, Shiotani A (2015) ERK2 mediates inner hair cell survival and decreases susceptibility to noise-induced hearing loss. Sci Rep 5:16839

    Article  CAS  Google Scholar 

  • Kurioka T, Lee MY, Heeringa AN, Beyer LA, Swiderski DL, Kanicki AC, Kabara LL, Dolan DF, Shore SE, Raphael Y (2016) Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus. Neuroscience 332:242–257

    Article  CAS  Google Scholar 

  • Lassmann H, van Horssen J, Mahad D (2012) Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 8:647–656

    Article  CAS  Google Scholar 

  • Lauer AM, Dent ML, Sun W, Xu-Friedman MA (2019) Effects of non-traumatic noise and conductive hearing loss on auditory system function. Neuroscience 407:182–191

    Article  CAS  Google Scholar 

  • Lee DL, Strathmann FG, Gelein R, Walton J, Mayer-Proschel M (2012) Iron deficiency disrupts axon maturation of the developing auditory nerve. J Neurosci 32:5010–5015

    Article  CAS  Google Scholar 

  • Liberman MC, Liberman LD, Maison SF (2015) Chronic conductive hearing loss leads to cochlear degeneration. PLoS ONE 10:e0142341

    Article  Google Scholar 

  • Liu J, Dietz K, DeLoyht JM, Pedre X, Kelkar D, Kaur J, Vialou V, Lobo MK, Dietz DM, Nestler EJ, Dupree J, Casaccia P (2012) Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nat Neurosci 15:1621–1623

    Article  CAS  Google Scholar 

  • Liu K, Jiang X, Shi C, Shi L, Yang B, Shi L, Xu Y, Yang W, Yang S (2013) Cochlear inner hair cell ribbon synapse is the primary target of ototoxic aminoglycoside stimuli. Mol Neurobiol 48:647–654

    Article  CAS  Google Scholar 

  • Mendoza E, Miranda-Barrientos JA, Vazquez-Roque RA, Morales-Herrera E, Ruelas A, De la Rosa G, Flores G, Hernandez-Echeagaray E (2014) In vivo mitochondrial inhibition alters corticostriatal synaptic function and the modulatory effects of neurotrophins. Neuroscience 280:156–170

    Article  CAS  Google Scholar 

  • Naganuma H, Kawahara K, Tokumasu K, Satoh R, Okamoto M (2014) Effects of arginine vasopressin on auditory brainstem response and cochlear morphology in rats. Auris Nasus Larynx 41:249–254

    Article  Google Scholar 

  • Nelson KR, Gilmore RL, Massey A (1988) Acoustic nerve conduction abnormalities in Guillain-Barre syndrome. Neurology 38:1263–1266

    Article  CAS  Google Scholar 

  • Prendergast G, Tu W, Guest H, Millman RE, Kluk K, Couth S, Munro KJ, Plack CJ (2018) Supra-threshold auditory brainstem response amplitudes in humans: test-retest reliability, electrode montage and noise exposure. Hear Res 364:38–47

    Article  Google Scholar 

  • Puel JL, Pujol R, Tribillac F, Ladrech S, Eybalin M (1994) Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity. J Comp Neurol 341:241–256

    Article  CAS  Google Scholar 

  • Pujol R, Lenoir M, Robertson D, Eybalin M, Johnstone BM (1985) Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells. Hear Res 18:145–151

    Article  CAS  Google Scholar 

  • Qi Y, Yu S, Du Z, Qu T, He L, Xiong W, Wei W, Liu K, Gong S (2019) Long-term conductive auditory deprivation during early development causes irreversible hearing impairment and cochlear synaptic disruption. Neuroscience 406:345–355

    Article  CAS  Google Scholar 

  • Richardson RT, O'Leary S, Wise A, Hardman J, Clark G (2005) A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support. Hear Res 204:37–47

    Article  CAS  Google Scholar 

  • Schimmang T, Tan J, Muller M, Zimmermann U, Rohbock K, Kopschall I, Limberger A, Minichiello L, Knipper M (2003) Lack of Bdnf and TrkB signalling in the postnatal cochlea leads to a spatial reshaping of innervation along the tonotopic axis and hearing loss. Development 130:4741–4750

    Article  CAS  Google Scholar 

  • Shepherd RK, Colreavy MP (2004) Surface microstructure of the perilymphatic space: implications for cochlear implants and cell- or drug-based therapies. Arch Otolaryngol Head Neck Surg 130:518–523

    Article  Google Scholar 

  • Sinclair JL, Fischl MJ, Alexandrova O, Hebeta M, Grothe B, Leibold C, Kopp-Scheinpflug C (2017) Sound-evoked activity influences myelination of brainstem axons in the trapezoid body. J Neurosci 37:8239–8255

    Article  CAS  Google Scholar 

  • Starr A, Michalewski HJ, Zeng FG, Fujikawa-Brooks S, Linthicum F, Kim CS, Winnier D, Keats B (2003) Pathology and physiology of auditory neuropathy with a novel mutation in the MPZ gene (Tyr145-%3eSer). Brain 126:1604–1619

    Article  Google Scholar 

  • Tagoe T, Barker M, Jones A, Allcock N, Hamann M (2014) Auditory nerve perinodal dysmyelination in noise-induced hearing loss. J Neurosci 34:2684–2688

    Article  CAS  Google Scholar 

  • van Loon MC, Ramekers D, Agterberg MJ, de Groot JC, Grolman W, Klis SF, Versnel H (2013) Spiral ganglion cell morphology in guinea pigs after deafening and neurotrophic treatment. Hear Res 298:17–26

    Article  Google Scholar 

  • Wan G, Gomez-Casati ME, Gigliello AR, Liberman MC, Corfas G (2014) Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma. Elife. https://doi.org/10.7554/eLife.03564

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by a GSK Japan Research Grant 2019 and a JSPS KAKENHI grant (Grant Number 19K24052) (both to T.K).

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0374, Japan

    Takaomi Kurioka, Sachiyo Mogi & Taku Yamashita

  2. Bio-Imaging Center, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, Japan

    Manabu Tanaka

Authors
  1. Takaomi Kurioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sachiyo Mogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manabu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taku Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TK designed the experiments. TK, SM, MT and TY performed the experiments and analyzed the data. TK wrote the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Takaomi Kurioka.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethics Committee of the Kitasato University School of Medicine (2019–085).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kurioka, T., Mogi, S., Tanaka, M. et al. Activity-Dependent Neurodegeneration and Neuroplasticity of Auditory Neurons Following Conductive Hearing Loss in Adult Mice. Cell Mol Neurobiol 41, 31–42 (2021). https://doi.org/10.1007/s10571-020-00829-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-020-00829-y

Keywords

Search

Navigation