Surgery-induced neuroinflammatory transcriptional programs in medial prefrontal cortex of mice during early phase of perioperative neurocognitive disorders

PeerJ. 2024 Dec 3:12:e18664. doi: 10.7717/peerj.18664. eCollection 2024.

Abstract

Patients receiving anesthesia and surgery may experience cognitive dysfunction, memory deficits, and mental disturbances, which are referred to as perioperative neurocognitive disorders (PND). The function of the medial prefrontal cortex (mPFC) is disrupted during early phase of PND. To gain insight into the mechanisms of PND, we collected mouse mPFC tissues 6 h post-surgery and performed RNA sequencing analysis. In total, 178 differentially expressed genes (DEGs) were identified, including 105 upregulated and 73 downregulated genes. Bioinformatic analysis highlighted the significant enrichment of these DEGs in several immune-related biological processes and signaling pathways, suggesting that pronounced neuroinflammatory transcriptional programming in the mPFC was evoked during early phase of PND. Interleukin-6 level increased in both serum and mPFC, while the mRNA levels of Il-6, Tnf-α, and Il-1β remained unchanged. Taken together, our findings suggest that a distinct and acute neuroinflammatory response in the mPFC is evoked after peripheral surgery, which might play a key role in the development of PND.

Keywords: Cognitive dysfunction; Medial prefrontal cortex; Neuroinflammation; RNA sequencing; Surgery.

MeSH terms

  • Animals
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurocognitive Disorders* / etiology
  • Neurocognitive Disorders* / genetics
  • Neurocognitive Disorders* / metabolism
  • Neuroinflammatory Diseases / genetics
  • Neuroinflammatory Diseases / immunology
  • Neuroinflammatory Diseases / metabolism
  • Perioperative Period
  • Prefrontal Cortex* / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta

Grants and funding

The research was supported by the Zhejiang Provincial Natural Science Foundation of China (LQ23H090013 and LBY22H270007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.