Role of MiR-34a/Bcl-2 apoptotic pathway in age-related hearing loss of mouse model

Abstract

Objective To explore the possible mechanism of miR-34a/Bcl-2 apoptotic pathway in the mouse model of age-related hearing loss. Methods A C57BL/6 mouse model of age-related hearing loss was conducted, and 4-week-old and 12-month-old mice were considered as the objects. The auditory brainstem response (ABR) was used to test the hearing function. The TdT-mediated dUTP nick end labeling (TUNEL) was used to observe the apoptosis of neuron in auditory cortex. The mRNA and protein levels of miR-34a, Bcl-2 and caspase 3 were detected by real-time PCR and Western bloting, respectively. Results The ABR showed that the hearing threshold level at 4, 8, 16, 32 kHz were higher in 12-month-old mice than in 4-week-old mice〔(80.0±2.5) dBHL vs. (32.0±4.5) dBHL, (74.0±3.5) dBHL vs. (51.0±1.2) dBHL, (86.0±4.6) dBHL vs. (51.0±3.5) dBHL, (87.0±6.6) dBHL vs. (56.0±1.5) dBHL, all P<0.05〕. Compared with 4-week-old mice, the total number of neurons in auditory cortex was decreased, the number of apoptosis neurons was increased, the expressions of miR-34a (t=6.02, P=0.001), Bax (t=6.51, P=0.012) and Caspase-3 (P=0.023) rised, and the expression of Bcl-2 (t=7.12, P=0.032) declined in 12-month-old mice. Conclusions The activation of miR-34a/Bcl-2 apoptotic pathway may be one of the mechanisms of age-related hearing loss. Key words: Presbycusis; Apoptosis