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Open Access Highly Accessed Research article

Biogenic amines and their metabolites are differentially affected in the Mecp2-deficient mouse brain

Nicolas Panayotis12*, Adeline Ghata12, Laurent Villard12 and Jean-Christophe Roux12

Author Affiliations

1 INSERM UMR_S 910, Unité de Génétique Médicale et Génomique Fonctionnelle, Equipe de Neurogénétique Humaine, France

2 Aix-Marseille Université, Faculté de Médecine de La Timone, Marseille, F-13385, France

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BMC Neuroscience 2011, 12:47  doi:10.1186/1471-2202-12-47

Published: 24 May 2011

Abstract

Background

Rett syndrome (RTT, MIM #312750) is a severe neurological disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Female patients are affected with an incidence of 1/15000 live births and develop normally from birth to 6-18 months of age before the onset of deficits in autonomic, cognitive, motor functions (stereotypic hand movements, impaired locomotion) and autistic features. Studies on Mecp2 mouse models, and specifically null mice, revealed morphological and functional alterations of neurons. Several functions that are regulated by bioaminergic nuclei or peripheral ganglia are impaired in the absence of Mecp2.

Results

Using high performance liquid chromatography, combined with electrochemical detection (HPLC/EC) we found that Mecp2-/y mice exhibit an alteration of DA metabolism in the ponto-bulbar region at 5 weeks followed by a more global alteration of monoamines when the disease progresses (8 weeks). Hypothalamic measurements suggest biphasic disturbances of norepinephrine and serotonin at pathology onset (5 weeks) that were found stabilized later on (8 weeks). Interestingly, the postnatal nigrostriatal dopaminergic deficit identified previously does not parallel the reduction of the other neurotransmitters investigated. Finally, dosage in cortical samples do not suggest modification in the monoaminergic content respectively at 5 and 8 weeks of age.

Conclusions

We have identified that the level of catecholamines and serotonin is differentially affected in Mecp2-/y brain areas in a time-dependent fashion.