Apoptotic cascades in the central auditory pathway after noise exposure

Noise exposure leads to dramatic physiological and anatomical changes within the central auditory pathway in addition to the well-known cochlear damage. Our group previously described a significant loss of neurons in different central auditory structures upon acoustic overstimulation. The aim of the present study was to investigate if declined neuronal cell density is caused by apoptotic mechanisms. Mice were noise-exposed (3 h, 5-20 kHz) at 115 dB SPL under anesthesia and investigated immediately after, and at 6 h, 24 h, or 7 days after the exposure (n=16). Unexposed animals were used as controls (n=5). Apoptotic cells were detected by fluorescence microscopy after terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL). TUNEL-positive cells were compared to cell density (diamidino phenylindole, DAPI) within the dorsal and ventral cochlear nucleus (VCN), and the central nucleus of the inferior colliculus (ICC). In all investigated auditory areas, TUNEL-positive cells were significantly increased after acoustic overstimulation. In the acute, 6-h, and 24-h groups, their numbers were significantly increased in the VCN, as well as in the 6-h, 24-h, and 7-day groups in the dorsal cochlear nucleus (DCN). In the ICC, TUNEL-positive cells were significantly increased in all exposed mice. In the VCN, the number of TUNEL-positive cells of the same grid size was three times the numbers in the ICC. Our results show that noise exposure induces apoptosis-related pathophysiological changes within the central auditory pathway in a time-dependent manner. This may represent potential therapeutic targets, and helps clarify the complex psychoacoustic phenomena of noise-induced hearing loss.