{
    "abstract": "Microglia are crucial for CNS homeostasis and are involved in a wide range of neurodegenerative and neuroinflammatory diseases. Systemic inflammation and infections can contribute to neurodegeneration later in life by affecting microglia. Like other innate immune cells, microglia can develop innate immune memory (IMM) in response to an inflammatory challenge, altering their response to subsequent stimuli. IMM can ameliorate or worsen CNS pathology, but it is unclear if IMM can be reversed to restore microglia functions. Here, we investigated whether microglia depletion-repopulation by inhibition of the colony-stimulating factor 1 receptor with BLZ945 reversed LPS-induced endotoxin tolerance in mice. Repopulated microglia displayed a reduced expression of homeostatic genes and genes related to mitochondrial respiration and TCA cycle metabolism and an increased expression of immune effector and activation genes. Nonetheless the blunted inflammatory gene response after LPS-preconditioning was retained after a depletion-repopulation cycle. Our study highlights the persistence of endotoxin tolerance in microglia after a depletion-repopulation cycle which might impact the potential effectiveness of strategies targeted at microglia depletion for clinical applications.",
    "authors": [
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Tiago",
            "initials": "T",
            "lastname": "Medeiros-Furquim"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Anneke",
            "initials": "A",
            "lastname": "Miedema"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Edwin",
            "initials": "E",
            "lastname": "Schilder"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Nieske",
            "initials": "N",
            "lastname": "Brouwer"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Inge R",
            "initials": "IR",
            "lastname": "Holtman"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
            "firstname": "Susanne M",
            "initials": "SM",
            "lastname": "Kooistra"
        },
        {
            "affiliation": "Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: b.j.l.eggen@umcg.nl.",
            "firstname": "Bart J L",
            "initials": "BJL",
            "lastname": "Eggen"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Inc.",
    "doi": "10.1016/j.bbi.2025.04.014",
    "journal": "Brain, behavior, and immunity",
    "keywords": [
        "BLZ945",
        "CSF1R",
        "CSF1R-inhibitor",
        "Depletion",
        "Endotoxin tolerance",
        "Innate immune memory",
        "Microglia",
        "Neuroinflammation",
        "Repopulation",
        "Sotuletinib"
    ],
    "methods": null,
    "publication_date": "2025-04-25",
    "pubmed_id": "40274001",
    "results": null,
    "title": "Microglia endotoxin tolerance is retained after enforced repopulation.",
    "xml": "<Element 'PubmedArticle' at 0x788506f36020>"
}