{
  "abstract": "Background: Perioperative neurocognitive disorders (PND) are recognized complications after anesthesia and surgery. Alzheimer-related brain states may increase vulnerability, but whether this susceptibility reflects a quantitatively larger or qualitatively distinct acute molecular response remains unclear. We addressed this question using a 5xFAD mouse cohort as an exploratory model of an amyloid-associated brain state.\n\nMethods: Hippocampal bulk RNA sequencing was performed in 4-month-old female wild-type (WT) and 5xFAD mice 24 h after control handling or combined isoflurane anesthesia and abdominal surgery ( n = 3 per factorial cell). DESeq2 was used to estimate genotype, exposure, and genotype-by-exposure effects. Additional sensitivity analyses included effect-size filtering, 12 leave-one-sample-out fits, edgeR quasi-likelihood modeling, and Cook’s-distance diagnostics. Mouse Hallmark gene-set enrichment analysis (GSEA), four marker-based cell-type-associated expression scores, and two public mouse transcriptomic datasets were used for pathway and external context.\n\nResults: WT and 5xFAD within-genotype contrasts identified 20 and 3 exposure-associated genes, respectively, at false discovery rate (FDR) < 0.05. The DESeq2 interaction identified 53 genes at FDR < 0.05; 37 also had |interaction log2FC| ≥ 1. All 53 had opposite-signed exposure-effect estimates in WT and 5xFAD mice, although separate within-genotype significance was not required. All retained their direction in 12 leave-one-out fits and in edgeR, and none exceeded the Cook’s-distance cutoff. However, no gene reached genome-wide FDR < 0.05 in edgeR, indicating method-dependent gene-level significance. Interaction-ranked GSEA identified 10 Hallmark pathways at FDR < 0.05, including positive interaction enrichment of TNF-alpha/NF-kappaB and interferon programs and negative interaction enrichment of oxidative phosphorylation and lipid/metabolic programs. All 10 retained direction and FDR < 0.05 in edgeR-ranked GSEA. None of the four marker-based scores had a significant interaction. No highlighted gene replicated at FDR < 0.05 in the external datasets.\n\nConclusions: In this small exploratory cohort, the 5xFAD genotype was associated with a directionally reorganized 24-h hippocampal transcriptional response to combined anesthesia and surgery. Pathway-level immune-metabolic interaction patterns were more robust than individual-gene significance. The findings do not establish a perioperative neurocognitive disorder phenotype, distinguish anesthesia from surgical effects, or validate biomarkers; they provide hypotheses for larger, longitudinal, behaviorally phenotyped, and experimentally validated studies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Shengjie Wang"
    },
    {
      "name": "Jiwei Song"
    },
    {
      "name": "Shaojun Sun"
    },
    {
      "name": "Renlong Xiao"
    },
    {
      "name": "Zhiyi Zhang"
    },
    {
      "name": "Junyao Zhang"
    },
    {
      "name": "Junyan Yao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9jndnk9gb16wy.bib",
  "cited_by": 0,
  "doi": "10.1186/s12864-026-13390-7",
  "fulltext_url": null,
  "id": "9jndnk9gb16wy",
  "issns": [
    "1471-2164"
  ],
  "landing_url": "https://link.springer.com/10.1186/s12864-026-13390-7",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2806|Anesthesia and Neurotoxicity Research"
    ]
  ],
  "openalex": "W7165193304",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/9jndnk9gb16wy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:08Z",
      "native_id": "10.1186/s12864-026-13390-7",
      "source": "crossref",
      "url": "https://link.springer.com/10.1186/s12864-026-13390-7"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Anesthesia and Neurotoxicity Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Genotype-dependent reconfiguration of hippocampal transcriptional responses to anesthesia/surgery at 24 h in 5xFAD mice: an exploratory interaction-based analysis",
  "title_text": "Genotype-dependent reconfiguration of hippocampal transcriptional responses to anesthesia/surgery at 24 h in 5xFAD mice: an exploratory interaction-based analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:08Z",
  "url": "https://research.draconitic.com/paper/9jndnk9gb16wy",
  "venue": "BMC Genomics",
  "versions": []
}