Fast green FCF prevents postoperative cognitive dysfunction via the downregulation of the P2X4 receptor in mice

Jun Liu1, Tao Gao2, Bin Zhou1

  • 1The First Affiliated Hospital of Ningbo University, Ningbo 315010, China.

Insights

Fast green FCF (FGF), a food dye, may prevent postoperative cognitive dysfunction (POCD) by reducing P2X4 receptor expression in the brain. This study shows FGF alleviates cognitive decline and neuroinflammation in mice, suggesting potential therapeutic use.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Postoperative cognitive dysfunction (POCD) is a significant concern in aged patients, with unclear pathological mechanisms.
  • Overexpression of the P2X4 receptor in the central nervous system (CNS) is linked to POCD onset.

Purpose of the Study:

  • To investigate if Fast green FCF (FGF) can prevent POCD by down-regulating CNS P2X4 receptor expression.
  • To explore the therapeutic potential of FGF for POCD.

Main Methods:

  • An animal model of POCD was established in mice using exploratory laparotomy under anesthesia.
  • FGF's effects on cognitive function, P2X4 receptor expression, microglial polarization, NF-κB phosphorylation, and pro-inflammatory cytokines were assessed.
  • The role of the P2X4 receptor was further examined using a specific antagonist (5-BDBD) and an allosteric modulator (ivermectin).

Main Results:

  • FGF significantly attenuated surgical-induced cognitive impairments and reduced P2X4 receptor expression in mice.
  • Blocking the P2X4 receptor with 5-BDBD demonstrated cognitive-enhancing effects in POCD mice.
  • FGF's effects were reversed by ivermectin, confirming P2X4 receptor involvement.
  • FGF inhibited M1 microglial polarization, decreased NF-κB phosphorylation, and reduced pro-inflammatory cytokine production.

Conclusions:

  • FGF exhibits anti-POCD effects by down-regulating P2X4 receptor-associated neuroinflammation.
  • These findings suggest FGF holds promise as a potential therapeutic agent for preventing POCD.

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