Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss

Jingjing Zhao, Gen Li, Xuan Zhao, Xin Lin, Yunge Gao, Nuno Raimundo, Geng Lin Li, Wei Shang, Hao Wu, Lei Song

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


AMP-activated protein kinase (AMPK) integrates the regulation of cell growth and metabolism. AMPK activation occurs in response to cellular energy decline and mitochondrial dysfunction triggered by reactive oxygen species (ROS). In aged Tg-mtTFB1 mice, a mitochondrial deafness mouse model, hearing loss is accompanied with cochlear pathology including reduced endocochlear potential (EP) and loss of spiral ganglion neurons (SGN), inner hair cell (IHC) synapses and outer hair cells (OHC). Accumulated ROS and increased apoptosis signaling were also detected in cochlear tissues, accompanied by activation of AMPK. To further explore the role of AMPK signaling in the auditory phenotype, we used genetically knocked out AMPKα1 as a rescue to Tg-mtTFB1 mice and observed: improved ABR wave I, EP and IHC function, normal SGNs, IHC synapses morphology and OHC survivals, with decreased ROS, reduced pro-apoptotic signaling (Bax) and increased anti-apoptotic signaling (Bcl-2) in the cochlear tissues, indicating that reduced AMPK attenuated apoptosis via ROS-AMPK-Bcl2 pathway in the cochlea. To conclude, AMPK hyperactivation causes accelerated presbycusis in Tg-mtTFB1 mice by redox imbalance and dysregulation of the apoptosis pathway. The effects of AMPK downregulation on pro-survival function and reduction of oxidative stress indicate AMPK serves as a target to rescue or relieve mitochondrial hearing loss.

Original languageEnglish (US)
Pages (from-to)5590-5611
Number of pages22
Issue number7
StatePublished - Apr 15 2020

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology


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