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Connexin 43 and hearing: Possible implications for retrocochlear auditory processing

Authors


  • Presented at Triologic Meeting, Miami Beach, Florida, U.S.A., January 26–28, 2012.

  • Grant Support: Triologic Career Development Award. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis

To examine the relationship between hearing and connexin 43, a dominant gap junctional protein in the central nervous system.

Study Design

Original research.

Methods

Connexin 43 heterozygous mice are used to assess its mutational effect on hearing. Results are compared to controls consisting of connexin 43, wild type and CBA/J mice. Hearing is assessed using auditory brainstem response and distortion product otoacoustic emissions tests. Distribution of connexin 43 in the organ of Corti and the retrocochlear auditory centers (eight nerve, cochlear nucleus, olivary complex, lateral lemniscus, inferior colliculus, respectively) is examined. Fluorescent markers are used to elucidate cell types.

Results

Mean click auditory brainstem response threshold for the young connexin 43 heterozygous mice (3–4 months) was 36.7 ± 12.6 dB compared to 25 ± 0 dB for control mice (P < 0.05). Mean threshold difference became more pronounced (68 ± 7.5 dB vs. 31 ± 2.2 dB) at 10 months (P < 0.05). Tonal auditory brainstem response testing showed elevated thresholds (>60 dB) at all frequencies (4–32 kHz) compared to the controls. Distortion product otoacoustic emissions (DPOAE) were present in all the mice, although the older connexin 43 heterozygous mice responded at higher thresholds. The pattern of connexin 43 immunoreactivity was distinctive from connexin 26 and 30, showing minimal presence in the organ of Corti but robustly present in the retrocochlear centers.

Conclusion

Connexin 43 heterozygous mice demonstrated greater degree of hearing loss compared to age-matched controls. It is abundantly found in the retrocochlear auditory centers. The mechanism of hearing loss in these mice does not appear to be related to hair cell loss.

Level of Evidence

N/A. Laryngoscope, 123:3185–3193, 2013

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