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In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by (13)C turnover from hyperpolarized [1-(13)C]acetate to [1-(13)C]acetylcarnitine

BACKGROUND: Acetate metabolism in skeletal muscle is regulated by acetylCoA synthetase (ACS). The main function of ACS is to provide cells with acetylCoA, a key molecule for numerous metabolic pathways including fatty acid and cholesterol synthesis and the Krebs cycle.METHODS: Hyperpolarized [1-(13)C]acetate prepared via dissolution dynamic nuclear polarization was injected intravenously at differ

Glutamatergic and GABAergic energy metabolism measured in the rat brain by (13) C NMR spectroscopy at 14.1 T

Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured (13)C incorporation into brain metabolites by dynamic (13)C nuclear magnetic resonance spect

The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts

C57BL/6 mice are the most widely used strain of laboratory mice. Using in vivo proton Magnetic Resonance Spectroscopy ((1)H MRS), we have repeatedly observed an abnormal neurochemical profile in the brains of both wild-type and genetically modified mice derived from the C57BL/6J strain, consisting of a several fold increase in cerebral glutamine and two fold decrease in myo-inositol. This striking

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice : an 18F-FDG PET study

UNLABELLED: We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are.METHODS: Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-t

MRS glucose mapping and PET joining forces : re-evaluation of the lumped constant in the rat brain under isoflurane anaesthesia

Although numerous positron emission tomography (PET) studies with (18) F-fluoro-deoxyglucose (FDG) have reported quantitative results on cerebral glucose kinetics and consumption, there is a large variation between the absolute values found in the literature. One of the underlying causes is the inconsistent use of the lumped constants (LCs), the derivation of which is often based on multiple assum

Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats

Type 1 diabetes can affect hippocampal function triggering cognitive impairment through unknown mechanisms. Caffeine consumption prevents hippocampal degeneration and memory dysfunction upon different insults and is also known to affect peripheral glucose metabolism. Thus we now characterized glucose transport and the neurochemical profile in the hippocampus of streptozotocin-induced diabetic rats

Glutathione Deficit Affects the Integrity and Function of the Fimbria/Fornix and Anterior Commissure in Mice : Relevance for Schizophrenia

BACKGROUND: Structural anomalies of white matter are found in various brain regions of patients with schizophrenia and bipolar and other psychiatric disorders, but the causes at the cellular and molecular levels remain unclear. Oxidative stress and redox dysregulation have been proposed to play a role in the pathophysiology of several psychiatric conditions, but their anatomical and functional con

Brain energy metabolism measured by (13)C magnetic resonance spectroscopy in vivo upon infusion of [3-(13)C]lactate

The brain uses lactate produced by glycolysis as an energy source. How lactate originated from the blood stream is used to fuel brain metabolism is not clear. The current study measures brain metabolic fluxes and estimates the amount of pyruvate that becomes labeled in glial and neuronal compartments upon infusion of [3-(13)C]lactate. For that, labeling incorporation into carbons of glutamate and

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

Alterations to brain homeostasis during development are reflected in the neurochemical profile determined noninvasively by (1)H magnetic resonance spectroscopy. We determined longitudinal biochemical modifications in the cortex, hippocampus, and striatum of C57BL/6 mice aged between 3 and 24 months . The regional neurochemical profile evolution indicated that aging induces general modifications of

Imaging of prolonged BOLD response in the somatosensory cortex of the rat

Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-ter

Deep thiopental anesthesia alters steady-state glucose homeostasis but not the neurochemical profile of rat cortex

Barbiturates are regularly used as an anesthetic for animal experimentation and clinical procedures and are frequently provided with solubilizing compounds, such as ethanol and propylene glycol, which have been reported to affect brain function and, in the case of (1)H NMR experiments, originate undesired resonances in spectra affecting the quantification. As an alternative, thiopental can be admi

Direct in vivo measurement of glycine and the neurochemical profile in the rat medulla oblongata

The medulla oblongata (MO) contains a high density of glycinergic synapses and a particularly high concentration of glycine. The aims of this study were to measure directly in vivo the neurochemical profile, including glycine, in MO using a spin-echo-based (1)H MRS sequence at TE = 2.8 ms and to compare it with three other brain regions (cortex, striatum and hippocampus) in the rat. Glycine was qu

Metabolic Flux and Compartmentation Analysis in the Brain In vivo

Through significant developments and progresses in the last two decades, in vivo localized nuclear magnetic resonance spectroscopy (MRS) became a method of choice to probe brain metabolic pathways in a non-invasive way. Beside the measurement of the total concentration of more than 20 metabolites, (1)H MRS can be used to quantify the dynamics of substrate transport across the blood-brain barrier b

Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice

Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine cons

CB₁ receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus

Cannabinoid CB₁ receptor (CB₁R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with ¹³C NMR isotopomer analysis whether CB₁Rs could have a local metabolic role in brain areas having high CB₁R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-¹³C]acetate, which is oxidized

Metabolic disturbances in diseases with neurological involvement

Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alteratio

Familial thrombophilia : clinical and molecular analysis of Swedish families with inherited resistance to activated protein C or protein S deficiency

This report describes the characterization of Swedish families with inherited resistance to activated protein C (APC resistance) and/or protein S deficiency, two genetic disorders associated with functional impairment of the protein C anticoagulant pathway. The APC resistance phenotype was linked to the factor V gene locus in a kindred with independent inheritance of APC resistance and protein S d

Activated protein C resistance : from phenotype to genotype and clinical practice

The anticoagulant protein C system is an important regulator of the blood coagulation process. Its targets are the procoagulant cofactors factor Va and factor VIIIa, which are cleaved and inactivated by activated protein C, protein S and intact factor V working as cofactors. Genetic defects of protein C or protein S were, together with antithrombin III deficiency, the previously established major

Non-Residential Capital Stock in Latin America, 1875-2008 : New Estimates and International Comparisons

We use a homogeneous method to estimate non-residential capital stock for Argentina, Brazil, Chile, and Mexico. Our estimates extend back to the late-nineteenth century, 50 years earlier than the present available estimates. Our estimates use the gross fixed capital formation data base (1850-1950). These data are linked with existing standardised national accounts for the region, such as those of