Biochem Biophys Res Commun. 2005 Dec 20; [Epub ahead of print]
Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism
Saywell V, Viola A, Confort-Gouny S, Le Fur Y, Villard L, Cozzone PJ.
INSERM U491, Faculte de Medecine la Timone, Marseille, France; Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille, France.
Abstract
Rett syndrome, a neurodevelopmental X-linked disorder, represents the most important genetic cause of severe mental retardation in the female population and results from a mutation in the gene encoding methyl-CpG-binding protein 2 (MECP2). We report here the first characterization of Mecp2-null mice, by in vivo magnetic resonance imaging and spectroscopy, delineating the cerebral phenotype associated with the lack of Mecp2. We performed a morphometric study that revealed a size reduction of the whole brain and of structures involved in cognitive and motor functions (cerebellum and motor cortex). Significant metabolic anomalies, including reduced N-acetylaspartate, myo-inositol, and glutamine plus glutamate, and increased choline levels were evidenced. These findings indicate that not only neuronal but also glial metabolism is affected in Mecp2-null mice. Furthermore, we uncovered an important reduction of brain ATP level, a hitherto undetected anomaly of energy metabolism that may reflect and contribute to cerebral injury and dysfunction.
Lay Summary
There are many non-invasive ways for scientists to examine the structure, function, and metabolism of living tissue. Magnetic Resonance Imaging (MRI) is a method of creating images of the inside of opaque organs in living organisms, to demonstrate pathological or other physiological alterations. One type of specialized MRI is known as Magnetic Resonance Spectroscopy (MRS), which produces a breadth of biochemical information about a region, thus providing an indication of its metabolic state. In this report, the authors use MRI and MRS to examine the overall brain structure and metabolic constituents in a mouse model of RTT. In agreement with previous studies, they describe a size reduction of the whole brain and of those brain regions responsible for various learning and movement functions. However, here they elegantly describe differences in levels of various metabolites known to play key roles in brain energy metabolism. These data identify novel cellular pathways which are altered in the brain of a mouse model of RTT, and thus provide a foundation for further examinations of these pathways. Indeed, the understanding the physiological and biochemical impacts of the MeCP2 mutation is essential for devising future potential therapeutic interventions.