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The P38MAPK/ATF2 signaling pathway is involved in PND in mice

Mengjiao Zhu1,2, Si Long3, Yizhi Tao2

  • 1Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Nanjing Road, Wuhan, 430030, Hubei Province, China.

Experimental Brain Research
|November 16, 2023
PubMed

Insights

Inhibition of the P38MAPK/ATF2 pathway reduces neuroinflammation and neuronal death in aged mice, improving cognitive function after surgery. This highlights a potential therapeutic target for perioperative neurocognitive disorder (PND).

Area of Science:

  • Neuroscience
  • Neuroinflammation
  • Cognitive Disorders

Background:

  • Microglia-mediated neuroinflammation in the hippocampus is linked to perioperative neurocognitive disorder (PND).
  • The P38MAPK signaling pathway is activated by stress and plays a role in inflammatory processes.

Purpose of the Study:

  • To investigate the role of the P38MAPK/ATF2 signaling pathway in the development of PND in aged mice.
  • To evaluate the therapeutic potential of inhibiting this pathway for PND.

Main Methods:

  • An aged mouse model of PND was established using tibial fracture surgery and isoflurane anesthesia.
  • Cognitive function was assessed using the open field test, Morris water maze (MWM), and fear conditioning test (FCT).
  • Hippocampal tissues were analyzed for inflammatory factors, apoptotic molecules, microglial activation (Iba-1), and neuronal survival after treatment with a P38MAPK inhibitor (SB239063).

Main Results:

  • PND mice exhibited cognitive impairment, increased hippocampal pro-inflammatory factors (IL-1β, TNF-α), proapoptotic molecules (caspase-3, bax), and microglial activation.
  • SB239063 treatment significantly reduced these markers and increased neuronal survival in the hippocampus.
  • Inhibition of the P38MAPK/ATF2 pathway attenuated neuroinflammation and neuronal apoptosis.

Conclusions:

  • The P38MAPK/ATF2 signaling pathway is implicated in hippocampal neuroinflammation and neuronal apoptosis contributing to PND in aged mice.
  • Inhibiting this pathway improves cognitive function in the PND model.
  • Targeting the P38MAPK/ATF2 pathway offers a potential therapeutic strategy for preventing or treating PND.
Keywords:
Microglial activationNeuroinflammationNeuronal apoptosisP38MAPK/ATF2 signaling pathwayPerioperative neurocognitive disorders

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