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We used<jats:italic>in vivo<\/jats:italic>plethysmography,<jats:italic>in vitro<\/jats:italic>electrophysiology, neuropharmacology, immunohistochemistry, and biochemistry to characterize the consequences of the<jats:italic>MECP2<\/jats:italic>mutation on breathing in wild-type (wt) and<jats:italic>Mecp2<\/jats:italic>-deficient (<jats:italic>Mecp2<\/jats:italic>-\/y) mice. At birth,<jats:italic>Mecp2<\/jats:italic>-\/y mice showed normal breathing and a normal number of medullary neurons that express tyrosine hydroxylase (TH neurons). At \u223c1 month of age, most<jats:italic>Mecp2<\/jats:italic>-\/y mice showed respiratory cycles of variable duration; meanwhile, their medulla contained a significantly reduced number of TH neurons and norepinephrine (NE) content, even in<jats:italic>Mecp2<\/jats:italic>-\/y mice that showed a normal breathing pattern. Between 1 and 2 months of age, all unanesthetized<jats:italic>Mecp2<\/jats:italic>-\/y mice showed breathing disturbances that worsened until fatal respiratory arrest at \u223c2 months of age. During their last week of life,<jats:italic>Mecp2<\/jats:italic>-\/y mice had a slow and erratic breathing pattern with a highly variable cycle period and frequent apneas. In addition, their medulla had a drastically reduced number of TH neurons, NE content, and serotonin (5-HT) content.<jats:italic>In vitro<\/jats:italic>experiments using transverse brainstem slices of mice between 2 and 3 weeks of age revealed that the rhythm produced by the isolated respiratory network was irregular in<jats:italic>Mecp2<\/jats:italic>-\/y mice but could be stabilized with exogenous NE. We hypothesize that breathing disturbances in<jats:italic>Mecp2<\/jats:italic>-\/y mice, and probably Rett patients, originate in part from a deficiency in noradrenergic and serotonergic modulation of the medullary respiratory network.<\/jats:p>","DOI":"10.1523\/jneurosci.4373-05.2005","type":"journal-article","created":{"date-parts":[[2005,12,14]],"date-time":"2005-12-14T23:03:18Z","timestamp":1134601398000},"page":"11521-11530","source":"Crossref","is-referenced-by-count":260,"title":["Mecp2 Deficiency Disrupts Norepinephrine and Respiratory Systems in Mice"],"prefix":"10.1523","volume":"25","author":[{"given":"Jean-Charles","family":"Viemari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K.","family":"Tryba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Saywell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Burnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Zanella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"B\u00e9vengut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Barthelemy-Requin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B. 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