Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex

Abstract

A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group). Therefore, a single noise exposure group has been investigated 7 (7-day-group-single) or 14 days (14-day-group-single) after noise exposure (3 h, 5-20 kHz, 115 dB SPL peak-to-peak). The double-exposure group received the same noise trauma for a second time 7 days after the initial exposure and was either TUNEL-stained immediately (7-day-group-double) or 1 week later (14-day-group-double) and data were compared to the corresponding single-trauma group as well as to an unexposed control group. It was shown that TUNEL increased immediately after the second noise exposure in AI-3 and stayed upregulated in the 14-day-group-double. A significant increase in TUNEL was also seen in the 14-day-group-double in vMGB, mMGB and AI-1. The present results show for the first time the influence of a repeated noise trauma on cell death mechanisms in thalamic and cortical structures and might contribute to the understanding of pathophysiological findings and psychoacoustic phenomena accompanying NIHL.

Apoptosis in the cochlear nucleus and inferior colliculus upon repeated noise exposure

“…The noise exposure paradigm has been described in recent publications of our group. [1819202324] Briefly, animals were exposed to a broadband flat spectrum noise (5–20 kHz) for 3 hours at 115 dB sound pressure level under anesthesia (6 mg/kg xylazine and 60 mg/kg ketamine) in a soundproof chamber (80 cm × 80 cm × 80 cm, minimal attenuation 60 dB). An amplifier (Tangent AMP-50; Eltax, Aulum, Denmark) and a DVD player were connected to loudspeakers (HTC 11.19; Visaton, Haan, Germany) placed above the animals’ heads.…”

“…Different groups of animals were investigated at various point of time after single or double noise exposure [Figure 1] analogous to earlier investigations. [2423] Eighteen animals of the experimental groups were noise exposed at day 0 and randomly assigned to the experimental groups. The single exposure group was exposed to the initial trauma only and either investigated at day 7 post-exposure (“7-day group-single”; n = 4 animals) or at day 14 post-exposure (“14-day group-single”; n = 5 animals).…”

“…Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) was performed according to earlier investigations. [2024] Briefly, on the day of investigation, animals were perfused via the left heart chamber with a fixative solution (4% paraformaldehyde). The skull was carefully opened to remove the brain.…”

“…[1920] Apoptosis after repeated noise trauma was already seen in the medial geniculate body and auditory cortex. [2124] The present study aimed at investigating the incidence of cell death after a second noise exposure in the VCN, DCN, and ICC. This might help to understand hearing pathologies in NIHL such as tinnitus or changed speech intelligibility.…”

Hyperbaric Oxygen Treatment Ameliorates Hearing Loss and Auditory Cortex Injury in Noise Exposed Mice by Repressing Local Ceramide Accumulation

“…Noise exposure has relation to complex manifestations such as hearing loss, tinnitus, reduced speech intelligibility and hyperacusis, which is largely ascribed to the neuronal damage in the central auditory pathway [1]. Including us, multiple labs have revealed the massive loss of cell density and apoptosis of neurons in higher auditory structures like medial geniculate body (MGB) and primary auditory cortex (A1) in the wake of intense noise exposure [1,2,3,4,5]. In this respect, keeping the auditory neurons from noise elicited damage stands out crucial for the improvement of the hearing performance.…”