Editor's ChoiceRett Syndrome

How Norepinephrine Neurons Contribute to Rett Syndrome

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Science Translational Medicine  07 Oct 2009:
Vol. 1, Issue 1, pp. 1ec1
DOI: 10.1126/scitranslmed.3000434

Rett syndrome, an X-linked developmental disorder of the brain, appears in girls before their first birthday, causing severe cognitive and movement problems. These girls carry a defective gene that codes for methyl-CpG-binding protein-2 (MeCP2), a protein present in all adult neurons. Its function is not entirely clear, but MeCP2, together with other proteins, binds to DNA in the promoter regions of genes, where it helps to turn transcription on and off. The identity of most of these MeCP2-regulated genes is not known, but clues can be gleaned from analyses of brains from patients and from a mouse model for Rett syndrome, which also carries a defective MeCP2 gene. Taneja et al. have examined, in the mouse model, a brain region called the locus ceruleus, the main source of neurons that use the neurotransmitter norepinephrine, which is known to be depleted in Rett patients. The authors found that these neurons are abnormally small but can actually fire at a higher frequency than normal. Further, the amounts of norepinephrine and its biosynthetic enzymes were lower in cells from mice without MeCP2, suggesting that one or more of the genes regulated by MeCP2 controls these several neuronal functions. The neurons in the locus ceruleus project to the cingulate cortex; these innervations were much reduced in the mutant mice. Norepinephrine-containing neurons seem to be particularly affected in both the Rett Syndrome mouse model and in patients, and indeed the dysfunctions in these neurons described by Taneja et al. could account for many of the difficulties of patients with Rett syndrome—including impaired breathing, which is controlled in part by the locus ceruleus, and Rett-associated deficits in cognitive function, which could be caused by the loss of norepinephrine modulation of cortical processing.

P. Taneja et al., Pathophysiology of locus ceruleus neurons in a mouse model of Rett Syndrome. J. Neurosci. 29, 12187–12195 (2009). http://www.jneurosci.org/cgi/content/full/29/39/12187

Citation: K.L. Kelner, How Norephinephrine Neurons Contribute to Rett Syndrome. Sci. Transl. Med. 1, 1ec1 (2009).

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