Elsevier

Neuroscience

Volume 161, Issue 3, 7 July 2009, Pages 915-925
Neuroscience

Sensory System
Research Paper
Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats

https://doi.org/10.1016/j.neuroscience.2009.03.072Get rights and content

Abstract

Exposure to intense noise induces apoptosis in hair cells in the cochlea. To identify the molecular changes associated with noise-induced apoptosis, we used quantitative real-time PCR to evaluate the changes in 84 apoptosis-related genes in cochlear samples from the sensory epithelium and lateral wall. Sprague–Dawley rats exposed to a continuous noise at 115 dB SPL for 2 h. The exposure caused a 40–60 dB threshold shift 4 h post-exposure that decreased to 20–30 dB 7 days post-exposure. These functional changes were associated with apoptotic markers including nuclear condensation and fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, eight genes were upregulated; three (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf family, three (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and one (Gadd45a) is a target of p53. At 7 days post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity.

Section snippets

Animals

Young Sprague–Dawley rats (210–300 g, male, Charles River Laboratories, Wilmington, MA, USA) were used. The procedures involving use and care of animals were reviewed and approved by the State University of New York at Buffalo Institutional Animal Care and Use Committee. The procedure minimized the number of animals used in this study as well as the suffering experienced by the animals.

Noise exposure

Rats were exposed for 2 h to a continuous noise (1–7 kHz) at 115 dB SPL (re 20 μPa). This noise level was

ABR threshold shifts

The average ABR thresholds measured pre-exposure and 4 h and 7-day post-exposure are presented in Fig. 1. The pre-exposure ABR thresholds varied from 30 to 45 dB between 5 and 40 kHz consistent with a previous study (Chen and Fechter, 2003). ABR thresholds at 4 h post-exposure were elevated significantly relative to pre-exposure thresholds (P<0.01). The average threshold shift across the frequency range was 50±9.3 dB (mean±SD). At 7 days post-exposure, thresholds had partially recovered leaving

Discussion

We exposed rats for 2 h to broadband noise at 115 dB SPL. The exposure caused a 40–60 dB hearing loss over a wide frequency range 4 h post-exposure. Morphological assessment of the cochlea at this time revealed a small portion (approximately 1% of the total hair cell population) of hair cells with apoptotic features, specifically condensed nuclei and TUNEL positive staining. At 7 days post-exposure, the hearing loss had decreased to 20–30 dB. Few hair cells with apoptotic features were seen at

Acknowledgments

The research was supported by R01DC00909101, R01DC006630, R03DC006181-03 and New Faculty Startup funds from College of Arts and Sciences, University at Buffalo. Presented in part at the 38th annual meeting of the Society for Neuroscience, held November 15–19, 2008, in Washington, DC.

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