Inositol | EPFL Graph Search

L'inositol () est une molécule organique cyclique, constituée de six atomes de carbone formant le cycle et de six groupements hydroxyles, chacun lié à un des carbones. Il existe neuf stéréoisomères possibles de l'inositol, le plus courant étant de loin le , qu'on trouve en abondance dans la nature et qu'on appelle simplement « inositol » par assimilation. Le joue un rôle important comme messager secondaire dans les cellules eucaryotes, notamment sous forme d'inositol phosphate, de phosphatidylinositol (PI) et de phosphatidylinositol phosphate (PIP). On le trouve facilement dans l'alimentation, en particulier dans les fruits et notamment dans les melons cantaloup et dans les oranges. Il est également présent chez les plantes sous forme d'hexaphosphate, appelé acide phytique, ou de sels de celui-ci, appelés phytates ; c'est notamment le cas des céréales riches en son. Le était jadis improprement appelé vitamine B7 bien qu'il ne s'agisse pas d'une vitamine car il est synthétisé par l

(1)H and (31)P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism

Corina Mihaela Berset, Cristina Ramona Cudalbu, Bernard Lanz, Veronika Rackayová

Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy ((1)H- and (31)P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by (31)P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.

Springer Verlag2016

Proton and phosphorus magnetic resonance spectroscopy of a mouse model of Alzheimer's disease

Patrick Aebischer, Cristina Ramona Cudalbu, Rolf Gruetter, Sharon Janssens, Hongxia Lei, Bernard Schneider, Lili Sun-Reimer

The development of new diagnostic criteria for Alzheimer's disease (AD) requires new in vivo markers reflecting early pathological changes in the brain of patients. Magnetic resonance (MR) spectroscopy has been shown to provide useful information about the biochemical changes occurring in AD brain in vivo. The development of numerous transgenic mouse models of AD has facilitated the evaluation of early biomarkers, allowing researchers to perform longitudinal studies starting before the onset of the pathology. In addition, the recent development of high-field animal scanners enables the measurement of brain metabolites that cannot be reliably quantified at lower magnetic fields. In this report, we studied a new transgenic mouse model of AD, the 5xFAD model, by in vivo proton and phosphorus MR spectroscopy. This model, which is characterized by an early-onset and a robust amyloid pathology, developed changes in the neurochemical profile, which are typical in the human disease, i.e., an increase in myo-inositol and a decrease in N-acetylaspartate concentrations, as early as in the 40th week of age. In addition, a significant decrease in the γ-aminobutyrate concentration was observed in transgenic mice at this age compared to controls. The pseudo-first-order rate constant of the creatine kinase reaction as well as relative concentrations of phosphorus-containing metabolites were not changed significantly in the 36 and 72-week old transgenic mice. Overall, these results suggest that mitochondrial activity in the 5 × FAD mice is not substantially affected but that the model is relevant for studying early biomarkers of AD.

Ios Press2012

Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease

Cristina Ramona Cudalbu, Veronika Rackayová

Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field (1)H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability.

2020

(1)H and (31)P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism

Corina Mihaela Berset, Cristina Ramona Cudalbu, Bernard Lanz, Veronika Rackayová

Springer Verlag2016