2. Academic Validation
  3. Fast green FCF prevents postoperative cognitive dysfunction via the downregulation of the P2X4 receptor in mice

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

  • Int Immunopharmacol. 2023 Jun 8;121:110462. doi: 10.1016/j.intimp.2023.110462.
Jun Liu 1,  Tao Gao 2,  Bin Zhou 1,  Xiaoxiao Xu 1,  Xiaojie Zhai 1,  Qinghuan Yao 1,  Xiaowei Chen 3,  Lin Liu 4,  Wei Cui 5,  Xiang Wu 1
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Ningbo University, Ningbo 315010, China.
  • 2 University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.
  • 3 Translational Medicine Center of Pain, Emotion and Cognition, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.
  • 4 Ningbo Women & Children's Hospital, Ningbo 315012, China.
  • 5 The First Affiliated Hospital of Ningbo University, Ningbo 315010, China; Translational Medicine Center of Pain, Emotion and Cognition, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China; Ningbo Kangning Hospital, Ningbo 315211, China.
PMID: 37301120 DOI: 10.1016/j.intimp.2023.110462
Abstract

Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 Receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 Receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 Receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10-12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 Receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 Receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 Receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor-κB (NF-κB), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD.

Keywords

Fast green FCF; NF-κB; Neuroinflammation; Postoperative cognitive dysfunction; the P2X4 receptor.

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