{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:52:00Z","timestamp":1789818720632,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T00:00:00Z","timestamp":1361318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Mice deficient in methyl\u2010CpG\u2010binding protein 2 (Mecp2; a model of Rett syndrome) display reduced CO<jats:sub>2<\/jats:sub> chemosensitivity, which may contribute to their breathing abnormalities. Patients and mice show reduced levels of brain 5\u2010HT, which is important in central chemosensitivity. It is not known whether increasing 5\u2010HT in this mouse model would improve their respiratory response to CO<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>We show, for the first time, that females heterozygous for the <jats:italic>Mecp2<\/jats:italic> mutation have a higher hypocapnic threshold for apnoeas <jats:italic>versus<\/jats:italic> wild\u2010type mice and that increasing 5\u2010HT in <jats:italic>Mecp2<\/jats:italic>\u2010null males, with citalopram, can correct CO<jats:sub>2<\/jats:sub> chemosensitivity, a finding that may be important clinically.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Mice deficient in the transcription factor methyl\u2010CpG\u2010binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO<jats:sub>2<\/jats:sub> chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for <jats:italic>Mecp2<\/jats:italic> show reduced levels of brain serotonin (5\u2010HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5\u2010HT in this mouse model would improve their respiratory response to CO<jats:sub>2<\/jats:sub>. Here we determined the apnoeic threshold in heterozygous Mecp2\u2010deficient female mice and examined the effects of blocking 5\u2010HT reuptake on the CO<jats:sub>2<\/jats:sub> response in <jats:italic>Mecp2<\/jats:italic>\u2010null male mice. Studies were performed in B6.129P2(C)\u2010<jats:italic>Mecp2<jats:sup>\u03c4m1.1Bird<\/jats:sup><\/jats:italic> null males and heterozygous females. In an <jats:italic>in situ<\/jats:italic> preparation, seven of eight Mecp2\u2010deficient heterozygous females showed arrest of phrenic nerve activity when arterial CO<jats:sub>2<\/jats:sub> was lowered to 3%, whereas the wild\u2010types maintained phrenic nerve amplitude at 53 \u00b1 3% of maximal. <jats:italic>In vivo<\/jats:italic> plethysmography studies were used to determine CO<jats:sub>2<\/jats:sub> chemosensitivity in null males. These mice were exposed sequentially to 1, 3 and 5% CO<jats:sub>2<\/jats:sub>. The percentage increase in minute ventilation in response to increased inspired CO<jats:sub>2<\/jats:sub> was less in <jats:italic>Mecp2<\/jats:italic><jats:sup>\u2212\/y<\/jats:sup> than in <jats:italic>Mecp2<\/jats:italic><jats:sup>+\/y<\/jats:sup> mice. Pretreatment with citalopram, a selective 5\u2010HT reuptake inhibitor (2.5 mg kg<jats:sup>\u22121<\/jats:sup>\u2002<jats:sc>i.p.<\/jats:sc>), 40 min prior to CO<jats:sub>2<\/jats:sub> exposure, in <jats:italic>Mecp2<\/jats:italic><jats:sup>\u2212\/y<\/jats:sup> mice resulted in an improvement in CO<jats:sub>2<\/jats:sub> chemosensitivity to wild\u2010type levels. These results suggest that decreased 5\u2010HT in Mecp2\u2010deficient mice reduces CO<jats:sub>2<\/jats:sub> chemosensitivity, and restoring 5\u2010HT levels can reverse this effect.<\/jats:p>","DOI":"10.1113\/expphysiol.2012.069872","type":"journal-article","created":{"date-parts":[[2012,11,24]],"date-time":"2012-11-24T04:20:22Z","timestamp":1353730822000},"page":"842-849","source":"Crossref","is-referenced-by-count":45,"title":["Increasing brain serotonin corrects CO<sub>2<\/sub> chemosensitivity in methyl\u2010CpG\u2010binding protein 2 (Mecp2)\u2010deficient mice"],"prefix":"10.1113","volume":"98","author":[{"given":"Marie A.","family":"Toward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Abdala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Knopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian F. 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