Noise-induced hearing loss alters hippocampal glucocorticoid receptor expression in rats

Abstract

Although the effects of intense noise exposure on the peripheral and central auditory pathway have been well characterized, its effects on non-classical auditory structures in the brain, such as the hippocampus, are less well understood. Previously, we demonstrated that noise-induced hearing loss causes a significant long-term reduction in hippocampal neurogenesis and cell proliferation. Given the known suppressive effects of stress hormones on neurogenesis, the goal of the present study was to determine if activation of the stress response is an underlying mechanism for the long-term reduction in hippocampal neurogenesis observed following noise trauma. To accomplish this, we monitored basal and reactive blood plasma levels of the stress hormone corticosterone in rats for ten weeks following acoustic trauma, and quantified changes in hippocampal glucocorticoid and mineralocorticoid receptors. Our results indicate that long-term auditory deprivation does not cause a persistent increase in basal or reactive stress hormone levels in the weeks following noise exposure. Instead, we observed a greater decline in reactive corticosterone release in noise-exposed rats between the first and tenth week of sampling compared to control rats. We also observed a significant increase in hippocampal glucocorticoid receptor expression which may cause greater hippocampal sensitivity to circulating glucocorticoid levels and result in glucocorticoid-induced suppression of neurogenesis, as well as increased feedback inhibition on the HPA axis. No change in mineralocorticoid receptor expression was observed between control and noise exposed rats. These results highlight the adverse effect of intense noise exposure and auditory deprivation on the hippocampus.

Keywords: Corticosterone; Glucocorticoid receptors; Hearing loss; Mineralocorticoid receptors; Neurogenesis; Noise-exposure.

Figure 1:

Experimental timeline. Animals were handled daily for one week prior to noise or sham exposure. Distortion product otoacoustic emissions (DPOAE) were assessed 24-hours post exposure to monitor hearing loss. Rats then underwent basal or reactive corticosterone sampling for a 10-week period. Hearing loss was again assessed 48 hours prior to sacrifice using auditory brainstem response (ABR) recordings. Following animal sacrifice, brain tissue was harvested and processed using immunohistochemical techniques.

Figure 2:

Distortion product otoacoustic emissions (DPOAEs), a measure of cochlear outer hair cell function, were assessed 24-hours post noise or sham exposure. DPOAEs were dramatically reduced in the left noise-exposed ears compared to unexposed ears at 6, 11 and 24 kHz, demonstrating cochlear damage from the noise exposure. (LE NF = left ear noise floor; RE NF = right ear noise floor).

Figure 3:

Auditory brainstem response (ABR) recordings were used to monitor permanent hearing loss following noise exposure at the end of the 10-week experimental timeline. The left noise-exposed ears demonstrated a significant threshold shift from 6–32 kHz compared to unexposed right ears, demonstrating the presence of a permanent hearing loss following the noise exposure protocol. (RE = right ear, LE = left ear). ABR thresholds in the left and right control ears were similar to the thresholds in the unexposed right ear.

Figure 4:

Baseline corticosterone levels were monitored pre and post noise exposure and over the 10-week sampling period in noise-exposed and control animals. No significant differences in basal corticosterone levels were observed between noise-exposed and control animals (Two-way RM-ANOVA, p > 0.05, n = 4). Data represent mean ± SEM.

Figure 5:

Reactive corticosterone levels before (pre), immediately following (post), and 1-hour after (1 hr post) exposure to 30-minutes of restraint were monitored over the 10-week sampling period in noise-exposed and control animals. (A) Reactive corticosterone levels were significantly elevated in noise-exposed rats 1-week post exposure (Two-way RM-ANOVA, p < 0.05, n = 5). (B-D) In contrast, in weeks 4–10, there was a trend for a reduction (i.e., blunting) of the stress response in the noise exposed group of animals compared to the controls; however, this difference was not statistically significant. Data represent mean ± SEM.

Figure 6:

Representative photomicrographs of hippocampal glucocorticoid receptor (GR) expression in noise-exposed (A, C) and control (B, D) rats. Cells immunopositive for GR can be seen spanning the length of the hippocampal dentate gyrus (DG). The arrows in panels A and B mark the location of the higher magnification images in panels C and D. Compared to control animals, unilaterally noise-exposed animals had a significant increase (~2 fold) in dentate gyrus GR expression (E; two-tailed t-test, p < 0.05). Data represent mean ± SEM.

Figure 7:

Representative photomicrographs of hippocampal mineralocorticoid receptor (MR) expression in noise-exposed (A, C) and control (B, D) rats. Cells immunopositive for MR can be seen spanning the length of the hippocampal dentate gyrus (DG). The arrows in panels A and B mark the location of the higher magnification images in panels C and D. No significant difference was observed in MR expression between noise-exposed and control animals (E; two-tailed t-test, p > 0.05). Data represent mean ± SEM.