The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss

Abstract

Hypothesis: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. Background: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. Methods: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. Results: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. Conclusion: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.