Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. - Structures Access content directly
Journal Articles Journal of Neuroscience Year : 2005

Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.

Laura B K Herzing
  • Function : Author


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.
Fichier principal
Vignette du fichier
11521.full.pdf (519.44 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-00287790 , version 1 (08-06-2021)



Jean-Charles Viemari, Jean-Christophe Roux, Andrew K Tryba, Véronique Saywell, Henri Burnet, et al.. Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.. Journal of Neuroscience, 2005, 25 (50), pp.11521-30. ⟨10.1523/JNEUROSCI.4373-05.2005⟩. ⟨hal-00287790⟩
417 View
37 Download



Gmail Facebook X LinkedIn More