Abstract
In this study, age related Cav1.3 expression in cochlea and auditory cortex of C57BL/6J male mice was evaluated. It was found that the expression of Cav1.3 in cochlea decreased with aging whereas this phenomenon was not observed in neuron of auditory cortex. The correlation between decreased expression of Cav1.3 and age-related hearing losses was studied in vitro, after Cav1.3 was knocked out, the rate of apoptosis of hair cells increased after being subjected to ROS stresses, accompanied with enhanced senescence. Further, Cav1.3 knock down also interfered with the electrophysiology of hair cells. The effect was further confirmed in vivo, after Cav1.3 knocked down by injection of AAV, hearing impairment was observed in C57BL/6J male mice subjected to senescence and this was accompanied by increased loss of hair cells in cochlea. The effect was further confirmed in 3D organ culture, increased loss of hair cells after Cav1.3 was knocked down under ROS stresses.Mechanistically, Cav1.3 knock out resulted in decreased intracellular calcium which subsequently reduced the inactivation of ROS from complex I, and finally resulted in increased intracellular ROS and enhanced senescence.Collectively, these findings confirmed that Cav1.3 could protect cells in auditory pathway from oxidative stresses, and decreased expression of Cav1.3 in auditory pathway could contribute to hearing losses by enhancement of calcium-mediated oxidative stress.
Highlights
Presbycusis or age-related hearing losses (ARHL) is the most common cause of hearing loss [1, 2]
Chen et al [13] reported that the expression of Cav1.3 in cochlea of C57BL/6J was gradually decreased when the mice got older accompanied by increased hearing threshold, which indicated a possible association between decreased expression of Cav1.3 and ARHL, but the underling mechanism is still unknown
Age-related expression of Cav1.3 was observed by immunofluorescence which indicated that its expression in auditory cortex increased before 16 weeks and decreased after 16 weeks (Figure 2A, 2B)
Summary
Presbycusis or age-related hearing losses (ARHL) is the most common cause of hearing loss [1, 2]. Cav1.3 is a voltage-gated calcium channel which plays an important role in diverse cell functions. It is mainly expressed in CNS, mediated persistent Ca2+ influx, sustain plateau potential, support peacemaking [9], and has a role in hair cell development [10,11,12]. Chen et al [13] reported that the expression of Cav1.3 in cochlea of C57BL/6J was gradually decreased when the mice got older accompanied by increased hearing threshold, which indicated a possible association between decreased expression of Cav1.3 and ARHL, but the underling mechanism is still unknown
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