Certain drugs and chemicals can damage the vestibular system, which is essential for hearing and balance. Prolonged use of toxic substances, such as certain antibiotics like streptomycin for tuberculosis relapses, or anticancer drugs, can damage the hair cells that form part of this system. In mammals, these cells have very limited regenerative capacity, so chronic exposure can lead to permanent sensory loss. Rather than dying immediately, hair cells can be “pushed out”,  a controlled process in which they leave the sensory epithelium and enter the fluid-filled cavity of the inner ear. Before this happens, subtle changes occur, including weakening of connections with nerve cells and disruption of specialised structures that maintain hair cell function.

 

A recent study, published in the Journal of Biomedical Science, led by the University of Barcelona and the Bellvitge Biomedical Research Institute (IDIBELL), with collaboration from CNAG, has identified the genetic mechanisms involved in the degradation of the vestibular system regarding the damage cause by these ototoxic compounds that affect the vestibule. The study found that one of the earliest and most consistent responses is the downregulation of hair cell-specific genes, which means a decrease in the activity of genes essential for hair cell function. This includes Atp2b2 and Xirp2, which help maintain the structure of the stereocilia, the tiny hair-like projections that detect sound and head movements; Nsg2, which is important for communication between hair cells and nerve cells; and Kcnab1 and Kcna10, which control ion channels that allow electrical signals to pass through the cells.
 
To uncover these early genetic changes, the study used RNA sequencing, a technique that measures the global gene expression and reveals which genes are activated or silenced in the tissues of the vestibular system. Marta Gut, Head of the Sequencing Unit at CNAG, together with our Functional Genomics Team members Anna Esteve-Codina and Beatriz Mur contributed with the sequencing and analysis of this project.
 
Using this approach, the study also showed that hair cells respond to chronic ototoxic stress by activating stress-related genes and adjusting processes such as cell adhesion, energy production, and protein handling. Understanding these early molecular changes provides valuable insights into the mechanisms behind hair cell loss and could help guide strategies to protect hearing and balance before permanent damage occurs. More specifically, these findings could also help improve the diagnosis of chronic vestibular ototoxicity and other pathologies related to the hair cells of the vestibular system. 
 
 
REFERENCE ARTICLE
Borrajo, M., Greguske, E.A., Maroto, A.F. et al. Early downregulation of hair cell (HC)-specific genes in the vestibular sensory epithelium during chronic ototoxicity. J Biomed Sci 32, 84 (2025). https://doi.org/10.1186/s12929-025-01180-4