2. Academic Validation
  3. GDF1 ameliorates cognitive impairment induced by hearing loss

GDF1 ameliorates cognitive impairment induced by hearing loss

  • Nat Aging. 2024 Mar 15. doi: 10.1038/s43587-024-00592-5.
Lina Pan 1,  Chunrui Li 1,  Lanxia Meng 1,  Guoxin Zhang 1,  Li Zou 2,  Ye Tian 1,  Sen Chen 3,  Yu Sun 3,  Dandan Su 1,  Xingyu Zhang 1,  Min Xiong 1,  Tingting Xiao 1,  Danhao Xia 1,  Zhengyuan Hong 4,  Zhentao Zhang 5 6
Affiliations

Affiliations

  • 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 PET-CT/MRI Center, Molecular Imaging Center, Renmin Hospital of Wuhan University, Wuhan, China.
  • 5 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China. zhentaozhang@whu.edu.cn.
  • 6 TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. zhentaozhang@whu.edu.cn.
PMID: 38491289 DOI: 10.1038/s43587-024-00592-5
Abstract

Hearing loss is associated with an increased risk of Alzheimer disease (AD). However, the mechanisms of hearing loss promoting the onset of AD are poorly understood. Here we show that hearing loss aggravates cognitive impairment in both wild-type mice and mouse models of AD. Embryonic growth/differentiation factor 1 (GDF1) is downregulated in the hippocampus of deaf mice. Knockdown of GDF1 mimics the detrimental effect of hearing loss on cognition, while overexpression of GDF1 in the hippocampus attenuates the cognitive impairment induced by deafness. Strikingly, overexpression of GDF1 also attenuates cognitive impairment in APP/PS1 transgenic mice. GDF1 activates Akt, which phosphorylates asparagine endopeptidase and inhibits asparagine endopeptidase-induced synaptic degeneration and Amyloid-β production. The expression of GDF1 is downregulated by the transcription factor CCAAT-enhancer binding protein-β. These findings indicate that hearing loss could promote AD pathological changes by inhibiting the GDF1 signaling pathway; thus, GDF1 may represent a therapeutic target for AD.

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