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Autophagy of Spinal Microglia Affects the Activation of Microglia through the PI3K/AKT/mTOR Signaling Pathway

Jingjuan Li1, Xin Cheng2, Dan Fu3

  • 1Department of Anesthesiology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China.

Neuroscience
|December 13, 2021
PubMed

Insights

Mild hypothermia improves ischemic spinal cord injury (ISCI) by enhancing autophagy and reducing microglia activation. This mechanism, involving PI3K/AKT/mTOR pathway inhibition, offers a potential therapeutic strategy for ISCI patients.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Surgical Research

Background:

  • Ischemic spinal cord injury (ISCI) can cause delayed paralysis after aortic aneurysm repair.
  • Mild hypothermia shows promise in improving ISCI outcomes, but its underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the protective mechanisms of mild hypothermia against ISCI in a rat model.
  • To explore the role of microglia activation and autophagy in ISCI and the effects of hypothermia.

Main Methods:

  • Induced ISCI in rats via aortic cross-clamping and treated with mild hypothermia.
  • Utilized an oxygen-glucose deprivation (OGD) model in BV-2 mouse microglia cells, treated with rapamycin.
  • Analyzed microglia activation, autophagy levels, and the PI3K/AKT/mTOR pathway in both models.

Main Results:

  • Mild hypothermia partially improved ISCI in rats, significantly inducing autophagy and reversing excessive microglia activation.
  • In vitro, OGD induced microglia activation and moderate autophagy; rapamycin enhanced autophagy and reversed microglia activation.
  • The PI3K/AKT/mTOR pathway was inhibited in both ISCI and OGD models, with further inhibition by hypothermia or rapamycin.

Conclusions:

  • Enhanced autophagy, potentially via PI3K/AKT/mTOR pathway inhibition, is a key mechanism by which mild hypothermia protects against ISCI.
  • Targeting autophagy presents a promising therapeutic avenue for mitigating ISCI.
Keywords:
autophagyischemic spinal cord ischemia (ISCI)microgliamild hypothermiarapamycinthe PI3K/AKT/mTOR signaling

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