The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Li, Shichang; Zheng, Hongwei; Xing, Zhimin; Liu, Yan; Han, Lin; Wang, Zijing; Yu, Lisheng

doi:10.1016/j.bjorl.2021.05.010

Cited by 5 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, innate immune response assessed as Iba1 + cell counts within the sensory epithelium at 7 dpn was not exacerbated, and instead was reduced, despite auditory physiological deficits in f/f cKO GR mice. Noise–dose divergent cochlear immune response was also found in investigations of circulating Cort related to circadian rhythm state, patterning levels of noise-induced damage with auditory physiology [ 20 , 99 , 100 ]. Some distinctions about the influence of GR expressed in supporting cells may be made: (1) supporting cell GR knockdown (f/+ heterozygous cKO GR), which could represent circadian time (based on available open receptors) distinct from control (no tamoxifen) mice, had typical physiological recovery from noise exposure and (2) supporting cell GR ablation was detrimental to auditory physiological recovery from noise exposure.…”

Section: Discussionmentioning

confidence: 92%

Conditional Ablation of Glucocorticoid and Mineralocorticoid Receptors from Cochlear Supporting Cells Reveals Their Differential Roles for Hearing Sensitivity and Dynamics of Recovery from Noise-Induced Hearing Loss

Barnes

Yee

Vetter

2023

IJMS

View full text Add to dashboard Cite

Endogenous glucocorticoids (GC) are known to modulate basic elements of cochlear physiology. These include both noise-induced injury and circadian rhythms. While GC signaling in the cochlea can directly influence auditory transduction via actions on hair cells and spiral ganglion neurons, evidence also indicates that GC signaling exerts effects via tissue homeostatic processes that can include effects on cochlear immunomodulation. GCs act at both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Most cell types in the cochlea express both receptors sensitive to GCs. The GR is associated with acquired sensorineural hearing loss (SNHL) through its effects on both gene expression and immunomodulatory programs. The MR has been associated with age-related hearing loss through dysfunction of ionic homeostatic balance. Cochlear supporting cells maintain local homeostatic requirements, are sensitive to perturbation, and participate in inflammatory signaling. Here, we have used conditional gene manipulation techniques to target Nr3c1 (GR) or Nr3c2 (MR) for tamoxifen-induced gene ablation in Sox9-expressing cochlear supporting cells of adult mice to investigate whether either of the receptors sensitive to GCs plays a role in protecting against (or exacerbating) noise-induced cochlear damage. We have selected mild intensity noise exposure to examine the role of these receptors related to more commonly experienced noise levels. Our results reveal distinct roles of these GC receptors for both basal auditory thresholds prior to noise exposure and during recovery from mild noise exposure. Prior to noise exposure, auditory brainstem responses (ABRs) were measured in mice carrying the floxed allele of interest and the Cre recombinase transgene, but not receiving tamoxifen injections (defined as control (no tamoxifen treatment), versus conditional knockout (cKO) mice, defined as mice having received tamoxifen injections. Results revealed hypersensitive thresholds to mid- to low-frequencies after tamoxifen-induced GR ablation from Sox9-expressing cochlear supporting cells compared to control (no tamoxifen) mice. GR ablation from Sox9-expressing cochlear supporting cells resulted in a permanent threshold shift in mid-basal cochlear frequency regions after mild noise exposure that produced only a temporary threshold shift in both control (no tamoxifen) f/fGR:Sox9iCre+ and heterozygous f/+GR:Sox9iCre+ tamoxifen-treated mice. A similar comparison of basal ABRs measured in control (no tamoxifen) and tamoxifen-treated, floxed MR mice prior to noise exposure indicated no difference in baseline thresholds. After mild noise exposure, MR ablation was initially associated with a complete threshold recovery at 22.6 kHz by 3 days post-noise. Threshold continued to shift to higher sensitivity over time such that by 30 days post-noise exposure the 22.6 kHz ABR threshold was 10 dB more sensitive than baseline. Further, MR ablation produced a temporary reduction in peak 1 neural amplitude one day post-noise. While supporting cell GR ablation trended towards reducing numbers of ribbon synapses, MR ablation reduced ribbon synapse counts but did not exacerbate noise-induced damage including synapse loss at the experimental endpoint. GR ablation from the targeted supporting cells increased the basal resting number of Iba1-positive (innate) immune cells (no noise exposure) and decreased the number of Iba1-positive cells seven days following noise exposure. MR ablation did not alter innate immune cell numbers at seven days post-noise exposure. Taken together, these findings support differential roles of cochlear supporting cell MR and GR expression at basal, resting conditions and especially during recovery from noise exposure.

show abstract

Section: Discussionmentioning

confidence: 92%

Conditional Ablation of Glucocorticoid and Mineralocorticoid Receptors from Cochlear Supporting Cells Reveals Their Differential Roles for Hearing Sensitivity and Dynamics of Recovery from Noise-Induced Hearing Loss

Barnes

Yee

Vetter

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Noise exposure alters clock gene expression ( Per1, Per2, Bmal1, and Rev-Erbα ) in the cochlea and the inferior colliculus, having direct implications for noise-induced hearing loss, but may also be relevant for dysregulated circadian rhythms in other brain regions and remote organs [ 493 ]. A differential effect of daytime versus nighttime noise exposure on several inflammatory cytokines with higher peak levels after daytime noise has also been observed [ 494 ].…”

Section: Pathophysiological Mechanisms Of Noise Exposurementioning

confidence: 99%

Health position paper and redox perspectives - Disease burden by transportation noise

Sørensen,

Pershagen,

Thacher

et al. 2024

Redox Biology

View full text Add to dashboard Cite

“…Targeting inflammatory signaling pathways and redox homeostasis can reduce noise-induced cochlear damage. [27,28] However, noise also increases BLB permeability, which should not be overlooked. The increased BLB permeability leads to the recruitment of more monocytes, further exacerbating the infiltration of inflammatory factors into the cochlea.…”

Section: Noise-induced Hearing Loss and Inflammationmentioning

confidence: 99%

“…Excessive acoustic stimulation causes hearing damage mainly due to inflammation and oxidative stress. Targeting inflammatory signaling pathways and redox homeostasis can reduce noise‐induced cochlear damage [27,28] . However, noise also increases BLB permeability, which should not be overlooked.…”

Section: Snhl and Inflammationmentioning

confidence: 99%

Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

Li,

Chen,

Lin

et al. 2023

Brain-X

View full text Add to dashboard Cite

Sensorineural hearing loss (SNHL) is a common otologic condition caused by damage to hair cells and spiral ganglion neurons that affects transmission pathways. Most of these cells cannot be regenerated, and there has been no breakthrough in regeneration techniques for inner ear cells. SNHL has a high incidence rate and can cause a variety of clinical symptoms, greatly impacting people's daily lives. With limited clinical treatments, the search for critical targets is urgent. Studies have shown that inflammation is prevalent in the pathogenesis of SNHL and plays a significant role in it. Inflammation is a normal body defense response, and a systemic anti‐inflammatory approach is undesirable. It is crucial for us to identify potential targets of inflammation in SNHL and take measures specifically targeting those targets with minimal systemic impact. This paper firstly describes the role of inflammation in various types of SNHL and then provides an overview of the interactions between inflammation and cochlear immunity, cochlear microcirculation, vascular spasm, and glutamate metabolism and finally comprehensively examines the feasibility of targets in these interactions. This paper is expected to facilitate the development of targeted anti‐inflammation for SNHL and provide strategies and approaches for treating clinical SNHL.

show abstract

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Cited by 5 publications

References 21 publications

Conditional Ablation of Glucocorticoid and Mineralocorticoid Receptors from Cochlear Supporting Cells Reveals Their Differential Roles for Hearing Sensitivity and Dynamics of Recovery from Noise-Induced Hearing Loss

Conditional Ablation of Glucocorticoid and Mineralocorticoid Receptors from Cochlear Supporting Cells Reveals Their Differential Roles for Hearing Sensitivity and Dynamics of Recovery from Noise-Induced Hearing Loss

Health position paper and redox perspectives - Disease burden by transportation noise

Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

Contact Info

Product

Resources

About