{
  "abstract": "Perioperative exposure to the volatile anesthetic isoflurane (ISO) during surgery (OP) has been associated with cognitive and olfactory deficits and may increase the risk of Alzheimer’s disease (AD). Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, contributes to disease pathogenesis through disrupted lipid homeostasis. However, whether ISO/OP interacts with APOE genotype to influence neurological vulnerability remains unclear. Young adult, presymptomatic humanized APOE4 and APOE3 knock-in mice underwent laparotomy under 2 h of ISO anesthesia. Microglia and astrocytes were isolated from the olfactory bulb (OB) and hippocampus (HI) for lipidomic profiling. Awake in vivo OB recordings assessed neuronal excitability and network activity, while ex vivo patch-clamp recordings assessed synaptic transmission in the OB and HI. On day 7, APOE4/ISO/OP glia showed greater lipid perturbations than APOE3/ISO/OP glia. In vivo recordings revealed genotype-dependent alterations in OB excitability and network operation, while patch-clamp recordings identified altered excitatory and inhibitory synaptic transmission in the OB and HI. APOE4/ISO/OP mice exhibited persistent odor memory deficits, transient olfactory sensitivity loss, early motor impairment, and delayed cognitive dysfunction. OB RNA sequencing identified alterations in calcium transport and metabolic pathways in APOE4 male mice at 90 days following exposure. Together, these findings demonstrate APOE4-dependent vulnerability to ISO/OP, characterized by glial lipid dysregulation, neural circuit dysfunction, and neurological impairment, and support a potential mechanistic contribution of altered lipid homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA",
    "Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA",
    "Center for Neurological Disease Research, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA",
    "Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA",
    "Department of Biomedical Sciences, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA",
    "Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA",
    "University of Maryland-Medicine Institute for Neuroscience Discovery (UM-MIND), University of Maryland School of Medicine, Baltimore, MD 21201, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yun Li",
      "orcid": "0000-0003-2040-4451"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuanyuan Ji",
      "orcid": "0000-0002-5258-3522"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Cosar Uzun",
      "orcid": "0000-0002-5950-9173"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Syed Taufiqul Islam"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Meigeng Hu",
      "orcid": "0009-0002-5265-0155"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Dan Zhao"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Yaping Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Hangnoh Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Zihui Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Jace W. Jones"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Shaolin Liu"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Junfang Wu",
      "orcid": "0000-0003-3338-7291"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4vt8mrw4tdtsp.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15212038",
  "fulltext_url": null,
  "id": "4vt8mrw4tdtsp",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/21/2038",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4vt8mrw4tdtsp.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:28Z",
      "native_id": "10.3390/cells15212038",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/21/2038"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2073-4409",
      "subfield": "cell-biology"
    }
  ],
  "title": "Isoflurane and Surgery Aggravate APOE4-Dependent Lipid Dysregulation, Neural Dysfunction, and Neurological Impairment in Male Mice",
  "title_text": "Isoflurane and Surgery Aggravate APOE4-Dependent Lipid Dysregulation, Neural Dysfunction, and Neurological Impairment in Male Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:28Z",
  "url": "https://research.draconitic.com/paper/4vt8mrw4tdtsp",
  "venue": "Cells",
  "versions": []
}