Hearing loss, including noise-induced hearing loss, is highly prevalent and severely hinders an individual's quality of life, yet many of the mechanisms that cause hearing loss are unknown. The pannexin (Panx) channel proteins, Panx1 and Panx3, are regionally expressed in many cell types along the auditory pathway, and mice lacking Panx1 in specific cells of the inner ear exhibit hearing loss, suggesting a vital role for Panxs in hearing. We proposed that Panx1 and/or Panx3 null mice would exhibit severe hearing loss and increased susceptibility to noise-induced hearing loss. Using the auditory brainstem response, we surprisingly found that Panx1−/− and Panx3−/− mice did not harbor hearing or cochlear nerve deficits. Furthermore, while Panx1−/− mice displayed no protection against loud noise-induced hearing loss, Panx3−/− mice exhibited enhanced 16- and 24-kHz hearing recovery 7 days after a loud noise exposure (NE; 12 kHz tone, 115 dB sound pressure level, 1 h). Interestingly, Cx26, Cx30, Cx43, and Panx2 were up-regulated in Panx3−/− mice compared with wild-type and/or Panx1−/− mice, and assessment of the auditory tract revealed morphological changes in the middle ear bones of Panx3−/− mice. It is unclear if these changes alone are sufficient to provide protection against loud noise-induced hearing loss. Contrary to what we expected, these data suggest that Panx1 and Panx3 are not essential for baseline hearing in mice tested, but the therapeutic targeting of Panx3 may prove protective against mid-high-frequency hearing loss caused by loud NE.
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The simultaneous binding of two antibodies to the same antigen (antibodies synergy or co-cooperativity) that elicit complement-mediated bactericidal activity is visualized with a model of a complex between Neisseria meningitides factor H binging protein (red cartoon) and monoclonal antibodies 12C1 (blue surface) and JAR5 (green surface). Monoclonal antibodies are schematically depicted with bars (colored light brown and yellow for heavy and light chains, respectively) in the background. Please see pp. 4699–4713 for more information. Picture generated and provided by Enrico Malito.
Differential effects of pannexins on noise-induced hearing loss Available to Purchase
Julia M. Abitbol, John J. Kelly, Kevin Barr, Ashley L. Schormans, Dale W. Laird, Brian L. Allman; Differential effects of pannexins on noise-induced hearing loss. Biochem J 15 December 2016; 473 (24): 4665–4680. doi: https://doi.org/10.1042/BCJ20160668
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