2. Academic Validation
  3. High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling

High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling

  • Metab Brain Dis. 2024 May 21. doi: 10.1007/s11011-024-01358-z.
Shu Liu 1 2 3 4,  Xu Yang 4 5,  Minghao Yuan 1 2 3 4,  Shengyuan Wang 1 2 3 4,  Haixia Fan 1 2 3 4,  Qian Zou 4,  Yinshuang Pu 4,  Zhiyou Cai 6 7 8 9 10
Affiliations

Affiliations

  • 1 Chongqing Medical University, 400042, Chongqing, China.
  • 2 Chongqing institute Green and Intelligent Technology, Chinese Academy of Sciences, 400714, Chongqing, Chongqing, China.
  • 3 Chongqing School, University of Chinese Academy of Sciences, 400714, Chongqing, Chongqing, China.
  • 4 Department of Neurology, Chongqing General Hospital, 400013, Chongqing, Chongqing, China.
  • 5 Department of Neurology, Affiliated Hospital of Southwest Medical University, 646000, Sichuan, China.
  • 6 Chongqing Medical University, 400042, Chongqing, China. caizhiyou@ucas.ac.cn.
  • 7 Chongqing institute Green and Intelligent Technology, Chinese Academy of Sciences, 400714, Chongqing, Chongqing, China. caizhiyou@ucas.ac.cn.
  • 8 Chongqing School, University of Chinese Academy of Sciences, 400714, Chongqing, Chongqing, China. caizhiyou@ucas.ac.cn.
  • 9 Department of Neurology, Chongqing General Hospital, 400013, Chongqing, Chongqing, China. caizhiyou@ucas.ac.cn.
  • 10 Department of Neurology, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, 400016, Chongqing, Chongqing, China. caizhiyou@ucas.ac.cn.
PMID: 38771412 DOI: 10.1007/s11011-024-01358-z
Abstract

A high-salt diet (HSD) has been associated with various health issues, including hypertension and cardiovascular diseases. However, recent studies have revealed a potential link between high salt intake and cognitive impairment. This study aims to investigate the effects of high salt intake on Autophagy, Tau Protein hyperphosphorylation, and synaptic function and their potential associations with cognitive impairment. To explore these mechanisms, 8-month-old male C57BL/6 mice were fed either a normal diet (0.4% NaCl) or an HSD (8% NaCl) for 3 months, and Neuro-2a cells were incubated with normal medium or NaCl medium (80 mM). Behavioral tests revealed learning and memory deficits in mice fed the HSD. We further discovered that the HSD decreased Autophagy, as indicated by diminished levels of the autophagy-associated proteins Beclin-1 and LC3, along with an elevated p62 protein level. HSD feeding significantly decreased insulin-like growth factor-1 receptor (IGF1R) expression in the brain of C57BL/6 mice and activated mechanistic target of rapamycin (mTOR) signaling. In addition, the HSD reduced synaptophysin and postsynaptic density protein 95 (PSD95) expression in the hippocampus and caused synaptic loss in mice. We also found amyloid β accumulation and hyperphosphorylation of Tau Protein at different loci both in vivo and in vitro. Overall, this study highlights the clinical significance of understanding the impact of an HSD on cognitive function. By targeting the IGF1R/mTOR/p70S6K pathway or promoting Autophagy, it may be possible to mitigate the negative effects of high salt intake on cognitive function.

Keywords

Autophagy; Cognitive impairment; High salt diet; IGF1R; Tau hyperphosphorylation; mTOR pathway.

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