View More View Less
  • 1 Department of Otolaryngology, Weifang City Hanting District People’s Hospital, Weifang 261100, Shandong, China
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Abstract

Background

Connexin 43 (Cx43) is the most ubiquitously expressed member of the family of connexins, constituting gap junctions and mediating cell communication, still its role in hearing loss has been little studied.

Methods

Immunohistochemistry was used to detect the expression pattern of Cx43. Spiral ganglia neurons (SGNs) and Corti co-culture were utilized to assay the re-innervation of hair cells by newborn SGNs. Gap19 was utilized to inhibit Cx43 hemichannels. Auditory brainstem responses (ABR) and endocochlear potential (E.P.) were measured to confirm the hearing loss.

Results

The expression of Cx43 in P14 mice was higher than in P0 and P28 (adult) mice, the earlier time point coinciding with the early inner ear development. Additionally, the growth and synapse generation of fibers were inhibited after Gap 19 treatment of the co-cultures of the Corti and SGNs from newborn mice. Furthermore, the inhibition of Cx43 could increase the ABR threshold and decrease E.P. level in postnatal mice, whereas such an effect was not observed in adult mice.

Conclusion

The function of Cx43 is critical during the early development of mouse cochlea but is dispensable in adult mice.

  • 1.

    Crowson MG, Hertzano R, Tucci DL. Emerging therapies for sensorineural hearing loss. Otol Neurotol 2017; 38(6): 792803.

  • 2.

    Wake M, Hughes EK, Poulakis Z, Collins C, Rickards FW. Outcomes of children with mild-profound congenital hearing loss at 7 to 8 years: a population study. Ear and Hearing 2004; 25(1): 18.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Nasralla HR, Gomez MVSG, Magalhaes AT, Bento RF. Important factors in the cognitive development of children with hearing impairment: case studies of candidates for cochlear implants. Int Arch Otorhinolaryngol 2014; 18(4): 35761.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Wei C, He Z, Kong W. Application of gene therapy in auditory system diseases. STEMedicine 2020; 1(1).

  • 5.

    Pohl U. Connexins: key players in the control of vascular plasticity and function. Physiol Rev 2020; 100(2): 52572.

  • 6.

    Wingard JC, Zhao H-B. Cellular and deafness mechanisms underlying connexin mutation-induced hearing loss – a common hereditary deafness. Front Cell Neurosci 2015; 9: 202–202.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, et al. . Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 2003; 72(2): 40818.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Liu W, Yang J. Preferentially regulated expression of connexin 43 in the developing spiral ganglion neurons and afferent terminals in post-natal rat cochlea. Eur J Histochem EJH 2015; 59(1).

    • Search Google Scholar
    • Export Citation
  • 9.

    Kim AH, Nahm E, Sollas A, Mattiace L, Rozental R. Connexin 43 and hearing: possible implications for retrocochlear auditory processing. The Laryngoscope 2013; 123(12): 318593.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Jovanovic S, Milenkovic I. Purinergic modulation of activity in the developing auditory pathway. Neurosci Bull 2020; 36: 12851298.

  • 11.

    Shen X, Dong Y, Xu Z, Wang H, Miao C, Soriano SG, et al. . Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiol: J Am Soc Anesthesiologists 2013; 118(3): 502–515.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Akil O, Oursler AE, Fan K, Lustig LR. Mouse auditory brainstem response testing. Bio Protoc 2016; 6(6): e1768.

  • 13.

    Kada S, Hamaguchi K, Ito J, Omori K, Nakagawa T. Bone marrow stromal cells accelerate hearing recovery via regeneration or maintenance of cochlear fibrocytes in mouse spiral ligaments. The Anatomical Rec 2020; 303(3): 47886.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Cai WJ, Wang ZL, Wei CF, Wu M, Zheng WP, Zhang HM, et al. . Prognostic evaluation of NANOG and OCT4 expression for posttransplantation hepatocellular carcinoma recurrence. J Cell Biochem 2019; 120(5): 841929.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Cohen-Salmon M, Maxeiner S, Krüger O, Theis M, Willecke K, Petit C. Expression of the connexin43-and connexin45-encoding genes in the developing and mature mouse inner ear. Cell Tissue Res 2004; 316(1): 1522.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Ahmad S, Chen S, Sun J, Lin X. Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mice. Biochem Biophysical Res Commun 2003; 307(2): 3628.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Walters BJ, Zuo J. Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration. Hear Res 2013; 297: 6883.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Lin JH-C, Lou N, Kang N, Takano T, Hu F, Han X, et al. . A central role of connexin 43 in hypoxic preconditioning. J Neurosci 2008; 28(3): 68195.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Nakase T, Söhl G, Theis M, Willecke K, Naus CC. Increased apoptosis and inflammation after focal brain ischemia in mice lacking connexin43 in astrocytes. The Am J Pathol 2004; 164(6): 206775.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Cherkas PS, Huang T-Y, Pannicke T, Tal M, Reichenbach A, Hanani M. The effects of axotomy on neurons and satellite glial cells in mouse trigeminal ganglion. Pain 2004; 110(1–2): 2908.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Hudspeth AJ. How the ear’s works work. Nature 1989; 341(6241): 397404.

  • 22.

    Hibino H, Kurachi Y. Molecular and physiological bases of the K+ circulation in the mammalian inner ear. Physiology 2006; 21(5): 33645.

  • 23.

    Kusakari J, Ise I, Comegys T, Thalmann I, Thalmann R. Effect of ethacrynic acid, furosemide, and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis. The Laryngoscope 1978; 88(1): 1237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Guo W, Lei C, Dengke L, Wei S, Shiming Y. Endocochlear potential and potassium concentration recording in minipig cochlea. J Otology 2012; 7(2): 1035.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Liu XZ, Xia XJ, Adams J, Chen ZY, Welch KO, Tekin M, et al. . Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet 2001; 10(25): 294551.

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 52 52 48
Full Text Views 4 4 4
PDF Downloads 4 4 4