BioSigRZ – ABRs & DPOAEs

Experimental animals are housed under tightly regulated conditions to standardize experiments and minimize the number of animals per experiment. Ultrasonic noise pollution is a potential problem in housing as it is inaudible for humans, and may thus remain undetected, whereas most laboratory animals can hear ultrasound. Compared with sounds audible to humans, ultrasonic noise has received much less attention, yet it can likewise induce physiological and behavioral effects in animals, including deleterious effects on welfare and on experimental reproducibility. In this study, we accidentally discovered that our mouse stable was polluted by an ultrasonic beep emitted by a radio. To investigate the impact of this beep, we tested under which conditions this beep would activate neurons in the inferior colliculus (IC) using the c-fos promotor in TRAP2 mice as a marker for activation. Exposure to the beep of the radio activated a band of neurons. A similar band was observed in the TRAP2 mice following exposure to a beep with the same frequency as the radio beep, and the location of the bands in both cases agreed with the tonotopic organization of the IC. A similar ultrasonic tone was observed in more than half of commercially available radios, indicating that the presence of a radio is likely to expose animals to a continuous tone that is inaudible to humans. Based on our findings, we therefore recommend that animal facilities routinely check for ultrasonic noise contamination to increase animal welfare and enhance study reproducibility.

Hearing relies on the lifelong stability of the actin core within hair cell stereocilia, yet the molecular mechanisms ensuring this stability are largely unknown. Here, we identify the transcription factor Sox3 as a key regulator of this core structure in mice. In the absence of Sox3, the stereocilia core progressively disassembles, leading to hearing loss and impaired mechanotransduction. Sox3-deficient stereocilia are also more susceptible to acoustic trauma and fail to repair structural gaps, whereas Sox3 overexpression confers resilience against noise-induced damage. Mechanistically, Sox3 deletion downregulates β-thymosin genes in hair cells, most prominently Tmsb10, an essential regulator of actin monomer availability. Depleting Tmsb10 recapitulates the core degeneration observed in Sox3-deficient hair cells, establishing the Sox3-Tmsb10 axis as a novel molecular mechanism governing the lifelong preservation of the stereocilia actin core. This regulatory pathway also represents a promising target for therapeutic intervention in noise-induced hearing loss.

Background/Objectives: Cisplatin-induced hearing loss (CIHL) is a major global health sequela of chemotherapy, affecting over half a million cancer patients annually. We previously reported that honokiol, a multifunctional molecule compatible with cisplatin, protects against CIHL and upregulates sirtuin 3. The sirtuin family is composed of seven highly conserved yet differentially expressed members that are critical enzymes for oxidative stress regulation in different cellular compartments. Therefore, this study aims to further verify the expression and upregulation of the entire sirtuin family during honokiol-mediated hearing protection against CIHL in a tumor-bearing mouse model. Methods:…