Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex

Abstract

It has previously been shown that acoustic overstimulation induces cell death and extensive cell loss in key structures of the central auditory pathway. A correlation between noise-induced apoptosis and cell loss was hypothesized for the cochlear nucleus and colliculus inferior. To determine the role of cell death in noise-induced cell loss in thalamic and cortical structures, the present mouse study (NMRI strain) describes the time course following noise exposure of cell death mechanisms for the ventral medial geniculate body (vMGB), medial MGB (mMGB), and dorsal MGB (dMGB) and the six histological layers of the primary auditory cortex (AI 1–6). Therefore, a terminal deoxynucleotidyl transferase dioxyuridine triphosphate nick-end labeling assay (TUNEL) was performed in these structures 24 h, 7 days, and 14 days after noise exposure (3 h, 115 dB sound pressure level, 5–20 kHz), as well as in unexposed controls. In the dMGB, TUNEL was statistically significant elevated 24 h postexposure. AI-1 showed a decrease in TUNEL after 14 days. There was no statistically significant difference between groups for the other brain areas investigated. dMGB’s widespread connection within the central auditory pathway and its nontonotopical organization might explain its prominent increase in TUNEL compared to the other MGB subdivisions and the AI. It is assumed that the onset and peak of noise-induced cell death is delayed in higher areas of the central auditory pathway and takes place between 24 h and 7 days postexposure in thalamic and cortical structures.

Acute Noise Exposure Is Associated With Intrinsic Apoptosis in Murine Central Auditory Pathway

“…Immunohistochemistry has identified apoptosis as one of main factors responsible for the above changes. Moreover, the time course of cell death supported the histological findings (Coordes et al, 2012 ; Fröhlich et al, 2017 ). A few studies investigated changes in the gene expression of the auditory brain in response to hearing loss.…”

“…Our results implied degenerative process occurring after noise exposure. Our most important finding was that the degeneration was detectable immediately after finishing acoustic trauma, which was shown for the first time in these kinds of experiments (Gröschel et al, 2010 , 2011 , 2014 ; Coordes et al, 2012 ; Fröhlich et al, 2017 ).…”

“…The hearing thresholds recovered partially over 1 week, and the animals were left with a stable mean permanent threshold shift of 38 dB between 4 and 20 kHz (Gröschel et al, 2011 ). Moreover, several other earlier studies reported that identical treatment caused the development of spontaneous neuronal hyperactivity (possibly related to tinnitus) as well as an acute and long-term upregulation in calcium activity and cellular degeneration in auditory brain structures (Gröschel et al, 2010 , 2011 , 2014 ; Coordes et al, 2012 ; Fröhlich et al, 2017 ). Our results demonstrated upregulation of Bcl2a1a gene expression immediately after acoustic trauma in all investigated structures, whereas the protein levels were reduced at least in the auditory brainstem.…”

“…Studies of the peripheral and central auditory system have shown the impact of noise on auditory tissues already within 1 h after exposure, being progressive for weeks and months. The degenerative effects are most prominent in cochlear outer hair cells followed by inner hair cells, supporting cells and further delayed negative effect along the central auditory pathway (Hamernik et al, 1984 ; Yang et al, 2004 ; Gröschel et al, 2010 ; Meltser et al, 2010 ; Coordes et al, 2012 ; Bohne et al, 2017 ; Fröhlich et al, 2017 ). Several studies investigated the expression of different cell death-related genes during cochlear degeneration to give insight into the underlying mechanisms.…”

“…In total, nine animals (trauma group) were anesthetized (60 mg/kg ketamine and 6 mg/kg xylazine) and noise-exposed in a soundproof chamber (0.8 × 0.8 × 0.8 m, minimal attenuation 60 dB) for 3 h to broadband white noise (5–20 kHz) at 115 dB sound pressure level (SPL). The selected noise trauma paradigm is in accordance with what is known about the hearing range of mice (≥1 and ≤100 kHz) and people (≥20 Hz and ≤20 kHz), covering the mouse low-frequency hearing range, and is based on our earlier studies on cellular degeneration and detection of cell death mechanisms after noise exposure to ensure similar experimental conditions (Heffner and Heffner, 2007 ; Gröschel et al, 2010 ; Reynolds et al, 2010 ; Coordes et al, 2012 ; Fröhlich et al, 2017 ). Noise was delivered binaurally by speakers (HTC 11.19; Visaton, Haan, Germany) placed above the animal's head.…”