Whole brain mapping of glutamate distribution in adult and old primates at 11.7T

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Energy defects in Huntington's disease: Why “in vivo” evidence matters

International audienceHuntington's disease (HD) is an inherited progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea), cognitive deficits and psychiatric disturbances. The most striking neuropathological change in HD is the early atrophy of the striatum. While the disease progresses, other brain structures also degenerate, including the cerebral cortex. Changes are also seen outside the brain, in particular weight loss/cachexia despite high dietary intake. The disease is caused by an abnormal expansion of a CAG repeat in the gene encoding the huntingtin protein (Htt). This mutation leads to the expression of a poly-glutamine stretch that changes the biological functions of mutant Htt (mHtt). The mechanisms underlying neurodegeneration in HD are not totally elucidated. Here, we discuss recent results obtained in patients, animal and cellular models suggesting that early disturbance in energy metabolism at least in part associated with mitochondrial defects may play a central role, even though all data are not congruent, possibly because most findings were obtained in cell culture systems or using biochemical analyses of post mortem tissues from rodent models. Thus, we put a particular focus on brain imaging studies that could identify biomarkers of energy defects in vivo and would be of prime interest in preclinical and clinical trials testing the efficacy of new therapies targeting energy metabolism in HD

Patient motivation ranked by caregivers at continuous positive airway pressure initiation is predictive of adherence and 1-year therapy termination rate

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Complementarity of gluCEST and 1^1H‐MRS for the study of mouse models of Huntington's disease

International audienceIdentification of relevant biomarkers is fundamental to understand biological processes of neurodegenerative diseases and to evaluate therapeutic efficacy. Atrophy of brain structures has been proposed as a biomarker, but it provides little information about biochemical events related to the disease. Here, we propose to identify early and relevant biomarkers by combining biological specificity provided by 1H‐MRS and high spatial resolution offered by gluCEST imaging. For this, two different genetic mouse models of Huntington's disease (HD)—the Ki140CAG model, characterized by a slow progression of the disease, and the R6/1 model, which mimics the juvenile form of HD—were used. Animals were scanned at 11.7 T using a protocol combining 1H‐MRS and gluCEST imaging. We measured a significant decrease in levels of N‐acetyl‐aspartate, a metabolite mainly located in the neuronal compartment, in HD animals, and the decrease seemed to be correlated with disease severity. In addition, variations of tNAA levels were correlated with striatal volumes in both models. Significant variations of glutamate levels were also observed in Ki140CAG but not in R6/1 mice. Thanks to its high resolution, gluCEST provided complementary insights, and we highlighted alterations in small brain regions such as the corpus callosum in Ki140CAG mice, whereas the glutamate level was unchanged in the whole brain of R6/1 mice. In this study, we showed that 1H‐MRS can provide key information about biological processes occurring in vivo but was limited by the spatial resolution. On the other hand, gluCEST may finely point to alterations in unexpected brain regions, but it can also be blind to disease processes when glutamate levels are preserved. This highlights in a practical context the complementarity of the two methods to study animal models of neurodegenerative diseases and to identify relevant biomarker

MRI investigation of internal defects in potato tubers with particular attention to rust spots induced by water stress

International audiencePotato quality is a major concern for both producers and customers. However, potato tubers are affected by various forms of internal damage with no external symptoms, leading to substantial economic losses. MRI was used as a non-invasive and quantitative method to evaluate internal defects in potato tubers and their evolution during storage. Rust spots, induced by water stress, were considered in particular. To this end, potato plants were cultivated both in the field and in pots and their water uptake was controlled. Following harvest and throughout the storage period, 3D images of tubers were recorded on a 1.5 T MRI scanner using a fast spin echo sequence. In parallel, the multi-exponential transverse relaxation times (T2) of the tubers were mapped in order to provide information on changes in water status and distribution at the subcellular level in rust spots and in healthy perimedullary regions. The occurrence of rust spots correlated with water conditions in greenhouse where water intake was carefully controlled. The number and individual volume of rust spots did not change during storage period, but they significantly increased with tuber size. Bi-exponential transverse relaxation revealed differences between healthy and damaged tissue

In vivo imaging of brain glutamate defects in a knock-in mouse model of Huntington's disease

International audienceHuntington's disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive and psychiatric symptoms. Atrophy of the striatum has been proposed for several years as a biomarker to assess disease progression in HD gene carriers. However, it does not provide any information about the biological mechanisms linked to HD pathogenesis. Changes in brain metabolites have been also consistently seen in HD patients and animal models using Magnetic Resonance Spectroscopy (MRS), but metabolite measurements are generally limited to a single voxel. In this study, we used Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) in order to map glutamate distribution in the brain of a knock-in mouse model (Ki140CAG) with a precise anatomical resolution. We demonstrated that both heterozygous and homozygous mice with pathological CAG repeat expansion in gene encoding huntingtin exhibited an atrophy of the striatum and a significant alteration of their metabolic profile in the striatum as compared to wild type littermate controls. The striatal decrease was then confirmed by gluCEST imaging. Surprisingly, CEST imaging also revealed that the corpus callosum was the most affected structure in both genotype groups, suggesting that this structure could be highly vulnerable in HD. We evaluated for the first time gluCEST imaging as a potential biomarker of HD and demonstrated its potential for characterizing metabolic defects in neurodegenerative diseases in specific regions

Toulouse dykes: reducing failure hazard combining structural reinforcement works and organization measures

Toulouse dykes include 16 km of various types of dykes and flood gates and stoplogs, belonging to several owners including Toulouse City and French State (DDT31) that own about 13 km. The Toulouse dykes Hazard Study has been made in 2014-2015. The study includes:

Toulouse dykes: reducing failure hazard combining structural reinforcement works and organization measures

Toulouse dykes include 16 km of various types of dykes and flood gates and stoplogs, belonging to several owners including Toulouse City and French State (DDT31) that own about 13 km. The Toulouse dykes Hazard Study has been made in 2014-2015. The study includes: