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- W2335154335 abstract "Rett syndrome (RTT) is a severe neurological disorder that is associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. RTT patients suffer from mental retardation and behavioral disorders, including heightened anxiety and state-dependent breathing irregularities, such as hyperventilation and apnea. Many symptoms are recapitulated by the <i>Mecp2</i>-null male mice (<i>Mecp2</i><sup>−/<i>y</i></sup>). To characterize developmental progression of the respiratory phenotype and explore underlying mechanisms, we examined <i>Mecp2</i><sup>−/<i>y</i></sup> and wild-type (WT) mice from presymptomatic periods to end-stage disease. We monitored breathing patterns of unrestrained mice during wake–sleep states and while altering stress levels using movement restraint or threatening odorant (trimethylthiazoline). Respiratory motor patterns generated by <i>in situ</i> working heart–brainstem preparations (WHBPs) were measured to assess function of brainstem respiratory networks isolated from suprapontine structures. Data revealed two general stages of respiratory dysfunction in <i>Mecp2</i><sup>−/<i>y</i></sup> mice. At the early stage, respiratory abnormalities were limited to wakefulness, correlated with markers of stress (increased fecal deposition and blood corticosterone levels), and alleviated by antalarmin (corticotropin releasing hormone receptor 1 antagonist). Furthermore, the respiratory rhythm generated by WHBPs was similar in WT and <i>Mecp2</i><sup>−/<i>y</i></sup> mice. During the later stage, respiratory abnormalities were evident during wakefulness and sleep. Also, WHBPs from <i>Mecp2</i><sup>−/<i>y</i></sup> showed central apneas. We conclude that, at early disease stages, stress-related modulation from suprapontine structures is a significant factor in the <i>Mecp2</i><sup>−/<i>y</i></sup> respiratory phenotype and that anxiolytics may be effective. At later stages, abnormalities of brainstem respiratory networks are a significant cause of irregular breathing patterns and central apneas." @default.
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- W2335154335 date "2011-09-30" @default.
- W2335154335 modified "2023-09-25" @default.
- W2335154335 title "Venture Capital Fund Performance" @default.
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- W2335154335 doi "https://doi.org/10.3905/jai.2011.14.2.024" @default.
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