1. Academic Validation
  2. Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

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

  • Neurobiol Dis. 2023 Oct 7:106320. doi: 10.1016/j.nbd.2023.106320.
Yue Liu 1 Huasong Zhang 2 Cong Fan 3 Feiyi Liu 3 Shaoying Li 3 Juanjuan Li 4 Huiying Zhao 3 Xianhai Zeng 4
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen 518172, China; The Fifth Clinical Institute, Zunyi Medical University, Zhuhai 519041, China. Electronic address: 764137782@qq.com.
  • 2 Department of Otolaryngology, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen 518172, China; Department of Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou 500001, China; Department of Otolaryngology, The Third Affiliated Hospital of Guangzhou Medical University. Electronic address: 764137782@qq.com.
  • 3 Department of Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou 500001, China.
  • 4 Department of Otolaryngology, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen 518172, China.
Abstract

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.

Keywords

Age-related hearing loss; Bcl2; Lipid metabolism; Neuropathy; Synaptic dysfunction.

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