{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:26:24Z","timestamp":1791293184867,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001819","name":"International Rett Syndrome Foundation","doi-asserted-by":"crossref","award":["IRSF-ANGEL#3101"],"award-info":[{"award-number":["IRSF-ANGEL#3101"]}],"id":[{"id":"10.13039\/100001819","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH-NINDS"],"award-info":[{"award-number":["NIH-NINDS"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 NS069220"],"award-info":[{"award-number":["R01 NS069220"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"\n Key points<\/jats:title>\n \n \n \n \n Rett syndrome is a prototypical neurological disorder characterised by abnormal breathing pattern and reduced ventilatory CO\n 2<\/jats:sub>\n sensitivity. Medullary astrocytes are a crucial component of central CO\n 2<\/jats:sub>\n \/pH chemosensitivity.\n <\/jats:p>\n <\/jats:list-item>\n \n \n This study tested the hypotheses that methyl\u2010CpG\u2010binding protein 2 (MeCP2) deficient medullary astrocytes are (i) unable to produce\/release appropriate amounts of lactate, and\/or (ii) unable to sense changes in\n \n \/[H\n +<\/jats:sup>\n ].\n <\/jats:p>\n <\/jats:list-item>\n \n \n We found no differences in tonic or hypoxia\u2010induced release of lactate from the ventral surface of the medulla oblongata or cerebral cortex between\n MeCP2<\/jats:italic>\n \u2010knockout and wild\u2010type mice.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Respiratory acidosis triggered robust [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n responses in wild\u2010type astrocytes residing near the ventral surface of the medulla oblongata. CO\n 2<\/jats:sub>\n \u2010induced [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n responses in astrocytes were dramatically reduced in conditions of MeCP2 deficiency.\n <\/jats:p>\n <\/jats:list-item>\n \n \n These data suggest that (i) \u2018metabolic\u2019 function of astrocytes in releasing lactate into the extracellular space is not affected by MeCP2 deficiency, and (ii) MeCP2 deficiency impairs the ability of medullary astrocytes to sense changes in\n \n \/[H\n +<\/jats:sup>\n ].\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n Rett syndrome, a prototypical neurological disorder caused by loss of function of the transcriptional regulator methyl\u2010CpG\u2010binding protein 2 (MeCP2) gene, is associated with a severely disordered breathing pattern and reduced ventilatory CO\n 2<\/jats:sub>\n sensitivity. In a mouse model of Rett syndrome (\n MeCP2<\/jats:italic>\n knockout), re\u2010introduction of the\n MeCP2<\/jats:italic>\n gene selectively in astrocytes rescues normal respiratory phenotype. In the present study we determined whether the metabolic and\/or signalling functions of astrocytes are affected by testing the hypotheses that in conditions of MeCP2 deficiency, medullary astrocytes are unable to produce\/release appropriate amounts of lactate or detect changes in\n \n \/[H\n +<\/jats:sup>\n ], or both. No differences in tonic or hypoxia\u2010induced release of lactate from the ventral surface of the medulla oblongata or cerebral cortex in brain slices of\n MeCP2<\/jats:italic>\n \u2010knockout and wild\u2010type mice were found. In brainstem slices of wild\u2010type mice, respiratory acidosis triggered robust elevations in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n in astrocytes residing near the ventral surface of the medulla oblongata. The magnitude of CO\n 2<\/jats:sub>\n \u2010induced [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n responses in medullary astrocytes was markedly reduced in conditions of MeCP2 deficiency, whereas [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n responses to ATP were unaffected. These data suggest that (i) metabolic function of astrocytes in releasing lactate into the extracellular space is not affected by MeCP2 deficiency, and (ii) MeCP2 deficiency impairs the ability of medullary astrocytes to sense changes in\n \n \/[H\n +<\/jats:sup>\n ]. Taken together with the evidence of severely blunted ventilatory sensitivity to CO\n 2<\/jats:sub>\n in mice with conditional\n MeCP2<\/jats:italic>\n deletion in astroglia, these data support the hypothesis of an important role played by astrocytes in central respiratory CO\n 2<\/jats:sub>\n \/pH chemosensitivity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp270369","type":"journal-article","created":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T10:55:20Z","timestamp":1431687320000},"page":"3159-3168","source":"Crossref","is-referenced-by-count":62,"title":["Impaired CO\n 2<\/sub>\n sensitivity of astrocytes in a mouse model of Rett syndrome"],"prefix":"10.1113","volume":"593","author":[{"given":"Egor","family":"Turovsky","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UK"},{"name":"Institute of Cell Biophysics Russian Academy of Sciences Pushchino Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastassios","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Abdala","sequence":"additional","affiliation":[{"name":"School of Physiology & Pharmacology University of Bristol Bristol BS8 1TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Gourine","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012104107"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.09.005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2004.09.011"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979736"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2275"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.8.1581"},{"key":"e_1_2_6_9_1","unstructured":"BissonnetteJM GargSK LioyDT KnoppSJ&MandelG(2012).Depletion of methyl\u2010CpG\u2010binding protein 2 (MeCP2) in astrocytes depresses chemosensitivity.Program No. 897.19.2012 Neuroscience Meeting Planner. 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