Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage

Abstract

Aminoglycoside-induced hair cell (HC) loss is one of the most important causes of hearing loss. After entering the inner ear, aminoglycosides induce the production of high levels of reactive oxygen species (ROS) that subsequently activate apoptosis in HCs. Citicoline, a nucleoside derivative, plays a therapeutic role in central nervous system injury and in neurodegenerative disease models, including addictive disorders, stroke, head trauma, and cognitive impairment in the elderly, and has been widely used in the clinic as an FDA approved drug. However, its effect on auditory HCs remains unknown. Here, we used HC-like HEI-OC-1 cells and whole organ explant cultured mouse cochleae to explore the effect of citicoline on aminoglycoside-induced HC damage. Consistent with previous reports, both ROS levels and apoptosis were significantly increased in neomycin-induced cochlear HCs and HEI-OC-1 cells compared to undamaged controls. Interestingly, we found that co-treatment with citicoline significantly protected against neomycin-induced HC loss in both HEI-OC-1 cells and whole organ explant cultured cochleae. Furthermore, we demonstrated that citicoline could significantly reduce neomycin-induced mitochondrial dysfunction and inhibit neomycin-induced ROS accumulation and subsequent apoptosis. Thus, we conclude that citicoline can protect against neomycin-induced HC loss by inhibiting ROS aggregation and thus preventing apoptosis in HCs, and this suggests that citicoline might serve as a potential therapeutic drug in the clinic to protect HCs.

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

“…Hearing loss could be caused by genetic factors, aging, chronic cochlear infections, ototoxic drugs, and noise exposure ( Zhu et al, 2018 ; Zhang Y. et al, 2019 ; Zhou et al, 2020 ). The reported mechanisms of hair cell damage mainly include mechanical shearing forces and oxidative damage to HCs ( Liu et al, 2016 ; He et al, 2017 ; Li et al, 2018 ; Zhong et al, 2020 ), eventually induce apoptotic cell death in HCs, especially the outer HCs of the basal turn. The loss of sensory hair cells is irreversible in adult mammals.…”

A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes

“…Sensorineural hearing loss is often induced by loss of HCs and SGNs in the inner ear cochlea (Liu et al, 2016(Liu et al, , 2019Zhong et al, 2020). HC transduces the sound waves into electric signals (Qi et al, 2019), while SGNs transfer these signals into the auditory cortex to have the hearing ability (Guo et al, 2016, 2019, 2020).…”

“…Various methods have been tried to establish the SSD animal model, among which cochlear ablation is the most often used method. Other ways include local injection of high dose of gentamicin or neomycin at early postnatal days to cochleae to mimic the congenital SSD to study the impact of monaural hearing deprivation on cortical development or deafening adult animals by injecting drugs to the middle ear, posterior canal, and round window at different ages to study the impact of sudden SSD on the trajectory changes of cortical, visual, and language processing (Jakob et al, 2016;Liu et al, 2016;Banakis Hartl et al, 2019;Cheng et al, 2019;Ding et al, 2020;Zhong et al, 2020).…”

Key Signaling Pathways Regulate the Development and Survival of Auditory Hair Cells

“…Hearing loss is caused by the irreversible loss of sensory HCs and degeneration of SGNs [14][15][16][17][18][19]. Middle ear lesions, noise, trauma, and genetic mutations can cause damage to HCs, which ultimately lead to hearing loss [20][21][22][23][24].…”