2. Academic Validation
  3. The study of beneficial effect and mechanism of propofol on TNF-α-induced p-Tau increase in HT22 hippocampal neurons

The study of beneficial effect and mechanism of propofol on TNF-α-induced p-Tau increase in HT22 hippocampal neurons

  • Neuroscience. 2025 Nov 10:587:81-89. doi: 10.1016/j.neuroscience.2025.09.048.
Shuai Gao 1,  Yifei Wang 2,  Zhihong Xu 3,  Minmin Zhu 4,  Zhipeng Meng 5,  Guanghui An 6,  Jiawei Chen 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Jing'an District Central Hospital of Shanghai, Fudan University, No.259 XiKang Road, Shanghai 200040, PR China.
  • 2 Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, PR China.
  • 3 Department of Intensive Care Medicine, Jing'an District Central Hospital of Shanghai, Fudan University, No.259 XiKang Road, Shanghai 200040, PR China.
  • 4 Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai 201399, PR China.
  • 5 Department of Anesthesiology, Huzhou Central Hospital, Affiliated Central Hospital of HuZhou University, No.1558 Sanhuan North Road, Huzhou, Zhejiang 313000, PR China. Electronic address: meng_zhipeng@126.com.
  • 6 Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, PR China. Electronic address: gh_An@163.com.
  • 7 Department of Anesthesiology, Jing'an District Central Hospital of Shanghai, Fudan University, No.259 XiKang Road, Shanghai 200040, PR China. Electronic address: Jiawei_chen@hotmail.com.
PMID: 41057130 DOI: 10.1016/j.neuroscience.2025.09.048
Abstract

Background: Tau Protein is a soluble microtubule-binding protein expressed in neurons. Abnormal post-translational modifications, such as hyperphosphorylation, are closely related to central nervous system inflammation and may lead to neuronal damage. Propofol has been shown to exert neuroprotective effects. In this study, we investigated the effects of propofol on TNF-α-induced p-Tau increase in hippocampal neurons and explored the underlying mechanisms.

Methods: HT22 hippocampal neurons were pretreated with propofol, and then stimulated with TNF-α. Cell viability was measured by cell counting kit-8 (CCK-8). The expression and phosphorylation of Tau, AMPK, Akt and the expression of SIRT3 were detected by Western blot. Mitophagy was detected through the Mitophagy detection kit and confocal imaging of LC3B localization.

Results: TNF-α enhanced Tau phosphorylation in a time- and dose-dependent manner, and significant effects were observed at 10 ng/mL for 2 h. Pretreatment with 25 μM propofol for 1 h effectively reduced TNF-α-induced Tau phosphorylation. TNF-α activated the phosphorylation of AMPK and Akt, which was attenuated by propofol pretreatment and by AMPK Inhibitor (Compound C) or Akt Inhibitor (MK2206). Meanwhile, TNF-α promoted Mitophagy and upregulated the expression of SIRT3, which was inhibited by propofol and by SIRT3 Inhibitor (3-TYP).

Conclusions: Propofol may attenuate TNF-α-induced p-Tau expression in HT22 cells through modulation of the AMPK/Akt signaling pathway, and may inhibit TNF-α-enhanced Mitophagy by affecting the AMPK/SIRT3 signaling pathway.

Keywords

HT22 hippocampal neurons; Mitophagy; Propofol; TNF-α; p-Tau.

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