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Tregs dysfunction aggravates postoperative cognitive impairment in aged mice.

Yile Zhou1, Huihui Ju1, Yan Hu1

  • 1Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Journal of Neuroinflammation
|March 18, 2023
PubMed
Summary

Blocking peripheral regulatory T cells, or Tregs, can improve surgery-induced cognitive dysfunction in aged mice. Aged Tregs play a key role in the development of postoperative cognitive dysfunction.

Keywords:
AgingBlood–brain barrierNeuroinflammationPostoperative cognitive dysfunctionRegulatory T cells

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Area of Science:

  • Neuroscience
  • Immunology
  • Gerontology

Background:

  • Neuroinflammation is a key factor in perioperative neurocognitive disorders.
  • Regulatory T cells (Tregs) are critical in modulating systemic immune responses.

Purpose of the Study:

  • To investigate the role of Tregs in the development of postoperative cognitive dysfunction (POCD).

Main Methods:

  • Surgery-induced neurocognitive disorder in aged mice.
  • Assessment of cognitive function using Morris water maze.
  • Analysis of splenic Tregs via RNA sequencing and flow cytometry.
  • Measurement of inflammatory factors and tight junction proteins.

Main Results:

  • Surgery impaired cognitive function, increased inflammatory factors, and elevated circulating Tregs in aged mice.
  • Treg transfusion from young mice partially restored the blood-brain barrier and alleviated POCD.
  • Aged Tregs showed altered gene expression in TNF signaling and cytokine interactions, with blunted function.
  • CD25 epitope blockade improved cognition, reduced hippocampal TNF-α, and protected the blood-brain barrier.

Conclusions:

  • Peripheral Tregs are essential in the development of POCD.
  • Blocking peripheral Tregs enhances surgery-induced cognitive function in aged mice.