{
    "abstract": "Obstructive sleep apnea (OSA) induces cognitive impairment that involves intermittent hypoxia (IH). Because OSA is recognized as a low-grade systemic inflammatory disease and only some patients develop cognitive deficits, we investigated whether IH-related brain consequences shared similar pathophysiology and required additional factors such as systemic inflammation to develop.\nNine-week-old male C57BL/6J mice were exposed to 1 day, 6 or 24 w of IH (alternating 21-5% FiO2 every 30 sec, 8 h/day) or normoxia. Microglial changes were assessed in the functionally distinct dorsal (dH) and ventral (vH) regions of the hippocampus using Iba1 immunolabeling. Then the study concerned dH, as vH only tended to be lately affected. Seven proinflammatory and anti-inflammatory cytokine messenger RNA (mRNA) were assessed at all time points using semiquantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Similar mRNA analysis was performed after 6 w IH or normoxia associated for the past 3 w with repeated intraperitoneal low-dose lipopolysaccharide or saline.\nChronic (6, 24 w) but not acute IH induced significant microglial changes in dH only, including increased density and morphological features of microglia priming. In dH, acute but not chronic IH increased IL-1\u03b2 and RANTES/CCL5 mRNA, whereas the other cytokines remained unchanged. In contrast, chronic IH plus lipopolysaccharide increased interleukin (IL)-6 and IL10 mRNA whereas lipopolysaccharide alone did not affect these cytokines.\nThe obstructive sleep apnea component intermittent hypoxia (IH) causes low-grade neuroinflammation in the dorsal hippocampus of mice, including early but transient cytokine elevations, delayed but long-term microglial changes, and cytokine response alterations to lipopolysaccharide inflammatory challenge. These changes may contribute to IH-induced cognitive impairment and pathological brain aging.",
    "authors": [
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Grenoble, F-38042, France.\nINSERM U1042, Laboratoire HP2, Grenoble, F-38042, France.",
            "firstname": "Emilie",
            "initials": "E",
            "lastname": "Sapin"
        },
        {
            "affiliation": "INSERM U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team SLEEP, F-69372, France.\nUniversit\u00e9 Claude Bernard Lyon 1, Lyon, F-69372, France.",
            "firstname": "Christelle",
            "initials": "C",
            "lastname": "Peyron"
        },
        {
            "affiliation": "CHU, H\u00f4pital Nord, Service de Physiologie Clinique et de l'Exercice, Saint-Etienne, F-42270, France.\nUniversit\u00e9 Jean Monnet, Saint-Etienne, F-42023, France.",
            "firstname": "Fr\u00e9d\u00e9ric",
            "initials": "F",
            "lastname": "Roche"
        },
        {
            "affiliation": "INSERM U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Team SLEEP, F-69372, France.\nUniversit\u00e9 Claude Bernard Lyon 1, Lyon, F-69372, France.",
            "firstname": "Nadine",
            "initials": "N",
            "lastname": "Gay"
        },
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Grenoble, F-38042, France.\nINSERM U836, Grenoble Institut des Neurosciences, \u00e9quipe 10, Grenoble, F-38042, France.",
            "firstname": "Carole",
            "initials": "C",
            "lastname": "Carcenac"
        },
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Grenoble, F-38042, France.\nINSERM U836, Grenoble Institut des Neurosciences, \u00e9quipe 10, Grenoble, F-38042, France.",
            "firstname": "Marc",
            "initials": "M",
            "lastname": "Savasta"
        },
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Grenoble, F-38042, France.\nINSERM U1042, Laboratoire HP2, Grenoble, F-38042, France.\nCHU, H\u00f4pital Michallon, Laboratoires du Sommeil et EFCR, Grenoble F-38043, France.",
            "firstname": "Patrick",
            "initials": "P",
            "lastname": "Levy"
        },
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Grenoble, F-38042, France.\nINSERM U1042, Laboratoire HP2, Grenoble, F-38042, France.\nCHU, H\u00f4pital Michallon, Addictologie, P\u00f4le Pluridisciplinaire de M\u00e9decine, Grenoble F-38043, France.",
            "firstname": "Maurice",
            "initials": "M",
            "lastname": "Dematteis"
        }
    ],
    "conclusions": "The obstructive sleep apnea component intermittent hypoxia (IH) causes low-grade neuroinflammation in the dorsal hippocampus of mice, including early but transient cytokine elevations, delayed but long-term microglial changes, and cytokine response alterations to lipopolysaccharide inflammatory challenge. These changes may contribute to IH-induced cognitive impairment and pathological brain aging.",
    "copyrights": "\u00a9 2015 Associated Professional Sleep Societies, LLC.",
    "doi": "10.5665/sleep.5042",
    "journal": "Sleep",
    "keywords": [
        "hippocampus",
        "inflammation",
        "intermittent hypoxia",
        "mice",
        "microglia"
    ],
    "methods": null,
    "publication_date": "2015-06-19",
    "pubmed_id": "26085297\n18250205\n8464434\n12586532\n18752879\n11706314\n18625666\n1779033\n12749549\n22670023\n23985418\n11509522\n15542074\n21753001\n15207349\n20002528\n11264318\n12950463\n23948880\n19404644\n21811879\n16712558\n9141509\n19075717\n15356039\n18759972\n12773326\n15994465\n19238810\n22073301\n20152109\n21531375\n24846772\n19506313\n25873766\n24332029\n21680945\n22187044\n24281245\n12074914\n9707404\n14975584\n21620385\n12122068\n8313151\n11166076\n19926287\n20193723\n16981890\n23210447\n21888951\n2731049\n22913604\n23570950\n21132050\n18495785\n21998606\n17220915\n12563281\n20002526\n11754995\n21665818\n24638131\n22889165\n23935246\n22143158\n19781994\n15489356\n21238488\n17855620\n16309961\n21966065\n23452941\n25093703\n14614919\n9108112\n23279636\n24326014",
    "results": null,
    "title": "Chronic Intermittent Hypoxia Induces Chronic Low-Grade Neuroinflammation in the Dorsal Hippocampus of Mice.",
    "xml": "<Element 'PubmedArticle' at 0x788504b6ed90>"
}