MRI and MRS in the living mice
MRI of the "Rett" mouse.
Using suitable imaging devices, it is possible to perform MRIs of the brain of anesthetized mice. For Rett syndrome, we were the first group to perform this kind of experiment. We tried to detect structural defects in the brain of the "Rett" mouse. The first study (Saywell et al. 2006) revealed a size reduction of the whole brain and of structures involved in cognitive and motor functions (cerebellum and motor cortex). Significant metabolic anomalies were also 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.
Magnetic resonance spectroscopy in the Mecp2-deficient brain.
We also performed, for the first time, a metabolomic study of brain extracts from Mecp2-null mice by using high-resolution magnetic resonance spectroscopy (Viola et al. 2007). A large number of individual water-soluble metabolites and phospholipids were quantified without prior selection for specific metabolic pathways. Results were interpreted in terms of Mecp2 gene deletion, brain cell function and brain morphology. This approach provided a "metabolic window" to brain characteristics in Mecp2-null mice, revealing (i) the first metabolic evidence of astrocyte involvement in RS (ii) a diminished potential of cells to grow, paralleled by globally reduced brain size and perturbed osmoregulation; (iii) alterations of the platelet activating factor (PAF) cycle in Mecp2-null mouse brains, where PAF is a bioactive lipid acting on neuronal growth, glutamate exocytosis and other processes; and (iv) a potentially altered neurotransmitter recycling.