The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease.

The present study evaluated the potential of using the phase of T 2 * weighted MR images to characterize myelination during brain development and pathology in rodents at 9.4 T. Phase contrast correlated with myelin content assessed by histology and suggests that most contrast between white and cortical gray matter is modulated by myelin. Ex vivo experiments showed that gray-white matter phase contrast remains unchanged after iron extraction. In dysmyelinated shiverer mice, phase imaging correlated strongly with myelin staining, showing reduced contrast between white and gray matter when compared to healthy controls. We conclude that highresolution phase images, acquired at high field, allow assessment of myelination and dysmyelination.© 2011 Elsevier Inc. All rights reserved. IntroductionThe assessment of myelination in healthy subjects and following injury in humans and in animal models is one of the ways to determine the degree of cerebral integrity or the degree of injury in case of white matter disease like multiple sclerosis. In newborns, myelination of the posterior limb of the internal capsule, when assessed at term equivalent, has been shown to be a very robust predictor of motor impairment (Cowan and de Vries, 2005). A simple technique that would access the degree of myelination of white matter would be very useful in mature animal models of white matter injury such as multiple sclerosis and in immature animal models of white matter injury such as periventricular leukomalacia as well as in human studies. There are various methods available: one approach consists of quantification of myelin bond and free water fractions by a multiexponential analysis of the T 2 decay (Beaulieu et al., 1998;MacKay et al., 1994;Whittall and MacKay, 1989;Lancaster et al., 2003). This is generally performed using a CarrPurcell-Meiboom-Gill (CPMG) or a Turbo Spin-Echo sequences with multiple echo times (Beaulieu et al., 1998). Due to specific absorption rate (SAR) (especially at high fields) and timing constraints, the T 2 decay curve is often not fully sampled for an accurate quantification. Recently, it has been shown that myelin water fraction can also be measured using a multi-exponential analysis of the T 2 * decay in multislice multiple echo gradient echo sequence (Du et al., 2007;Hwang et al., 2010). The resulting myelin water fractions are highly dependent on the constraints introduced on the multi-exponential fitting procedure (Hwang et al., 2010) and suffer from significant inaccuracies in regions close to air-tissue interfaces. An alternative approach of a multicomponent relaxation analysis using multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) (Deoni et al., 2008) was applied successfully on infants from 3 to 11 months to quantify myelination (Deoni et al., 2011). Magnetization transfer represents an alternative approach to quantify myelin with new approaches refining its modelization by characterizing individually the relaxation and exchange rates of the free water and macromolec...

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorder related to type 2 diabetes (T2D). The disease can evolve toward nonalcoholic steatohepatitis (NASH), a state of hepatic inflammation and fibrosis. There is presently no drug that effectively improves and/or prevents NAFLD/NASH/fibrosis. GLP-1 receptor agonists (GLP-1Ra) are effective in treating T2D. As with the endogenous gut incretins, GLP-1Ra potentiate glucose-induced insulin secretion. In addition, GLP-1Ra limit food intake and weight gain, additional beneficial properties in the context of obesity/insulin-resistance. Nevertheless, these pleiotropic effects of GLP-1Ra complicate the elucidation of their direct action on the liver. In the present study, we used the classical methionine-choline deficient (MCD) dietary model to investigate the potential direct hepatic actions of the GLP-1Ra liraglutide. A 4-week infusion of liraglutide (570 mg/kg/day) did not impact body weight, fat accretion or glycemic control in MCD-diet fed mice, confirming the suitability of this model for avoiding confounding factors. Liraglutide treatment did not prevent lipid deposition in the liver of MCD-fed mice but limited the accumulation of C16 and C24-ceramide/sphingomyelin species. In addition, liraglutide treatment alleviated hepatic inflammation (in particular accumulation of M1 pro-inflammatory macrophages) and initiation of fibrosis. Liraglutide also influenced the composition of gut microbiota induced by the MCD-diet. This included recovery of a normal Bacteroides proportion and, among the Erysipelotrichaceae family, a shift between Allobaculum and Turicibacter genera. In conclusion, liraglutide prevents accumulation of C16 and C24-ceramides/sphingomyelins species, inflammation and initiation of fibrosis

Background: Lipopolysaccharide (LPS) injection in the corpus callosum (CC) of rat pups results in diffuse white matter injury similar to the main neuropathology of preterm infants. The aim of this study was to characterize the structural and metabolic markers of acute inflammatory injury by high-field magnetic resonance imaging (MRI) magnetic resonance spectroscopy (MRS) in vivo. Methods: Twenty-four hours after a 1-mg/kg injection of LPS in postnatal day 3 rat pups, diffusion tensor imaging and proton nuclear magnetic spectroscopy (

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