Abstract:
Noise induced hearing loss is one of the leading causes for hearing loss in both developed and developing countries. Currently there are no effective treatments to restore hearing thresholds to their original levels once noise trauma has taken effect. Hearing devices only help to amplify sounds by mimicking the normal function of the auditory system, and thus rely on residual hearing thresholds. Previous studies have shown that adenosine and its receptor agonists have protective effects in various tissues and organs, including the cochlea, and thus hold therapeutic potential. Of focus in this study is the adenosine A1 receptor and its mechanisms of cochlear protection. We utilized both wildtype and selective A1AR knockout c57BL/6 mice to assess differences in expression levels of oxidative markers [mitochondrial SOD-1 and glutathione reductase] in response to acute noise trauma (2 hours of 8-16kHz narrowband noise). Auditory thresholds for transient clicks were measured before noise exposure and repeated 24 hours after to confirm the presence of a permanent threshold shift. The cochlear tissues were then extracted and sectioned for immunohistochemistry (1:200 dilution of SOD-1, 1:50 dilution of glutathione reductase). The sections were then viewed under a confocal microscope and semi-quantitative analysis was performed on different areas of interest within the cochlea, namely the inner hair cells, outer hair cells, spiral ligament, and the stria vascularis. Although statistically significant values were obtained when the group means were compared, due to the unrefined nature of methodology it cannot be stated that these results are indicative of any significant differences between wild type and knockout mice. This study provides insight into how a loss of function in the A1 receptor could affect cochlear protection against noise rather than previous studies which looked at increasing their functionality.
