2. Academic Validation
  3. High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression

  • Mol Brain. 2022 Jul 18;15(1):61. doi: 10.1186/s13041-022-00947-2.
Wen-Jiao Xue  # 1,  Cheng-Feng He  # 1,  Ren-Yuan Zhou  # 2,  Xiao-Die Xu 1,  Lv-Xuan Xiang 1,  Jian-Tao Wang 3,  Xin-Ru Wang 3,  Hou-Guang Zhou 4,  Jing-Chun Guo 5
Affiliations

Affiliations

  • 1 Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • 2 Department of Urology, Jing'an District Central Hospital, Fudan University, Shanghai, China.
  • 3 Department of Geriatric Neurology of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China.
  • 4 Department of Geriatric Neurology of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China. zhg7376@163.com.
  • 5 Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China. jingchunguo@shmu.edu.cn.
  • # Contributed equally.
PMID: 35850767 DOI: 10.1186/s13041-022-00947-2
Abstract

Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and Other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell Autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.

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