Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

• Published in: Neurobiology of disease Vol. 187; p. 106320
• Main Authors: Liu, Yue, Zhang, Huasong, Fan, Cong, Liu, Feiyi, Li, Shaoying, Li, Juanjuan, Zhao, Huiying, Zeng, Xianhai
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.10.2023; Elsevier
• Subjects: Age-related hearing loss; Bcl2; Lipid metabolism; Neuropathy; Synaptic dysfunction; Bcl2; Lipid metabolism; Neuropathy; Age-related hearing loss; Synaptic dysfunction
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2023.106320

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder. [Display omitted] •The absence of Bcl2 in the auditory cortex results in disruptions in lipid metabolism, diminished synaptic function, and neurodegeneration.•Lack of Bcl2 that promotes changes in hair cells, spiral ganglion cells, and nerve fibers abundance leads to age-related inner ear nerve obstruction and hearing loss.•The potential regulatory mechanisms of Bcl2 present an exciting opportunity for exploring novel therapeutic interventions in ARHL.