PMID:16354910

Citation	Viemari, JC, Roux, JC, Tryba, AK, Saywell, V, Burnet, H, Peña, F, Zanella, S, Bévengut, M, Barthelemy-Requin, M, Herzing, LB, Moncla, A, Mancini, J, Ramirez, JM, Villard, L and Hilaire, G (2005) Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J. Neurosci. 25:11521-30
Abstract	Rett syndrome is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein 2 (MECP2) gene and suffer from bioaminergic deficiencies and life-threatening breathing disturbances. We used in vivo plethysmography, in vitro electrophysiology, neuropharmacology, immunohistochemistry, and biochemistry to characterize the consequences of the MECP2 mutation on breathing in wild-type (wt) and Mecp2-deficient (Mecp2-/y) mice. At birth, Mecp2-/y mice showed normal breathing and a normal number of medullary neurons that express tyrosine hydroxylase (TH neurons). At approximately 1 month of age, most Mecp2-/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 Mecp2-/y mice that showed a normal breathing pattern. Between 1 and 2 months of age, all unanesthetized Mecp2-/y mice showed breathing disturbances that worsened until fatal respiratory arrest at approximately 2 months of age. During their last week of life, Mecp2-/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. In vitro 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 Mecp2-/y mice but could be stabilized with exogenous NE. We hypothesize that breathing disturbances in Mecp2-/y mice, and probably Rett patients, originate in part from a deficiency in noradrenergic and serotonergic modulation of the medullary respiratory network.
Links	PubMed Online version:10.1523/JNEUROSCI.4373-05.2005
Keywords	Animals; Disease Models, Animal; Humans; Male; Medulla Oblongata/physiopathology; Methyl-CpG-Binding Protein 2/deficiency; Methyl-CpG-Binding Protein 2/genetics; Methyl-CpG-Binding Protein 2/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Norepinephrine/antagonists & inhibitors; Norepinephrine/physiology; Respiratory Mechanics/genetics; Respiratory Mechanics/physiology; Respiratory System Abnormalities/genetics; Respiratory System Abnormalities/metabolism; Respiratory System Abnormalities/physiopathology; Rett Syndrome/genetics; Rett Syndrome/metabolism; Rett Syndrome/physiopathology
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