|
| ||
|
|
||
Brain Metabolism (brain + metabolism)
Selected AbstractsBrain metabolism of exogenous pyruvateJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Susana Villa Gonzalez Abstract Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3- 13C]pyruvate led to dose-dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3- 13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4- 13C]glutamate or [2- 13C]GABA from [3- 13C]pyruvate, but reduced formation of [4- 13C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3- 13C]lactate from [2- 13C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo, but that care must be taken to avoid the seizure-inducing effect of pyruvate given in large doses. [source] Neural correlates of memory in depression measured by brain perfusion SPECT at restPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2009Hideki Azuma md Aim:, Brain metabolism activated studies have indicated associations between memory and the anterior cingulate cortex and hippocampus in patients with depression. The aim of the present study was therefore to investigate memory function, measured as performance on the Wechsler Memory Scale,Revised (WMS-R), and its relationship to brain perfusion using single-photon emission computed tomography (SPECT) at rest in patients with depression. Methods:, The Hamilton Rating Scale for Depression (HAMD) and WMS-R were measured for 17 patients with depression by an independent clinical evaluation team. Voxel-based correlation analyses were performed with statistical parametric mapping at an extent threshold of 200 voxels. Associations were controlled for state and trait factors. Results:, WMS-R measurements of verbal, visual, and general memory were inversely correlated with brain perfusion in the right anterior cingulate cortex, left premotor cortices, and both regions, respectively. The HAMD directly correlated with brain perfusion in the right anterior cingulate cortex. Conclusion:, Brain perfusion SPECT measurements of the anterior cingulate cortex at rest were associated with the severity of depression and immediate memory scores measured with the WMS-R. [source] Brain metabolism in rett syndrome: Age, clinical, and genotype correlations,ANNALS OF NEUROLOGY, Issue 1 2009Alena Horská PhD Objective Brain metabolism, as studied by magnetic resonance spectroscopy (MRS), has been previously shown to be abnormal in Rett syndrome (RTT). This study reports the relation of MRS findings to age, disease severity, and genotype. Methods Forty RTT girls (1,14 years old) and 12 age-matched control subjects were examined. Single-voxel proton MRS of left frontal white matter was performed. Results NAA/Cr ratios decreased and myoinositol/Cr ratios increased with age in RTT patients (both p < 0.03), whereas these ratios were stable in control. The mean glutamate and glutamine/Cr ratio was 36% greater in RTT patients than in control (p = 0.043). The mean NAA/Cr ratio was 12.6% lower in RTT patients with seizures compared with those without seizures (p = 0.017). NAA/Cr ratios decreased with increasing clinical severity score (p = 0.031). Compared with patients with T158X, R255X, and R294X mutations, and C-terminal deletions, patients with the R168X mutation tended to have the greatest severity score (0.01 , p , 0.11) and the lowest NAA/Cr ratio (0.029 , p < 0.14). Interpretation Decreasing NAA/Cr and increasing myoinositol/Cr with age are suggestive of progressive axonal damage and astrocytosis in RTT, respectively, whereas increased glutamate and glutamine/Cr ratio may be secondary to increasing glutamate/glutamine cycling at the synaptic level. The relations between NAA/Cr, presence or absence of seizures, and disease severity suggest that MRS provides a noninvasive measure of cerebral involvement in RTT. Ann Neurol 2009;65:90,97 [source] Hypofrontality in schizophrenia: a meta-analysis of functional imaging studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2004K. Hill Objective:, Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. Method:, Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. Results:, Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. Conclusion:, Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture. [source] Regional cerebral brain metabolism correlates of neuroticism and extraversionDEPRESSION AND ANXIETY, Issue 3 2006Thilo Deckersbach Ph.D. Abstract Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based on the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the amygdala. Twenty healthy women completed an 18FFDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively. Depression and Anxiety 23:133,138, 2006. © 2006 Wiley-Liss, Inc. [source] Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphateEPILEPSIA, Issue 2008Janet L. Stringer Summary Fructose-1,6-diphosphate (FDP), an intracellular metabolite of glucose, has anticonvulsant activity in several models of acute seizures in laboratory animals. The anticonvulsant effect of FDP is most likely due to a direct effect since intraperitoneal and oral administration results in significant increases in brain levels. A number of mechanisms have been proposed for this action of FDP. One possibility is that peripheral administration of FDP results in changes in brain metabolism that are anticonvulsant. Glucose can be metabolized through the glycolytic or pentose phosphate pathway. There is evidence that the pentose phosphate pathway is more active in the brain than in other tissues, and that, in the presence of elevated levels of FDP, the majority of glucose is metabolized by the pentose phosphate pathway. The pentose phosphate pathway generates NADPH, which is used to reduce glutathione. The reduced form of endogenous glutathione has been shown to have anticonvulsant activity. Taken together, the data suggest a hypothesis that exogenously administered FDP gets into the brain and astrocytes where it increases the flux of glucose through the pentose phosphate pathway, generating additional NADPH for the reduction of glutathione. [source] Sensory gating in primary insomniaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010Ilana S. Hairston Abstract Although previous research indicates that sleep architecture is largely intact in primary insomnia (PI), the spectral content of the sleeping electroencephalographic trace and measures of brain metabolism suggest that individuals with PI are physiologically more aroused than good sleepers. Such observations imply that individuals with PI may not experience the full deactivation of sensory and cognitive processing, resulting in reduced filtering of external sensory information during sleep. To test this hypothesis, gating of sensory information during sleep was tested in participants with primary insomnia (n = 18) and good sleepers (n = 20). Sensory gating was operationally defined as (i) the difference in magnitude of evoked response potentials elicited by pairs of clicks presented during Wake and Stage II sleep, and (ii) the number of K complexes evoked by the same auditory stimulus. During wake the groups did not differ in magnitude of sensory gating. During sleep, sensory gating of the N350 component was attenuated and completely diminished in participants with insomnia. P450, which occurred only during sleep, was strongly gated in good sleepers, and less so in participants with insomnia. Additionally, participants with insomnia showed no stimulus-related increase in K complexes. Thus, PI is potentially associated with impaired capacity to filter out external sensory information, especially during sleep. The potential of using stimulus-evoked K complexes as a biomarker for primary insomnia is discussed. [source] ,-Synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipidsJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Mikhail Y. Golovko Abstract Previously, we demonstrated that ablation of ,-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown. In the present study, we examined the effect of Snca gene ablation on brain 22:6n-3 metabolism. We determined 22:6n-3 uptake and incorporation into brain phospholipids by infusing awake, wild-type and Snca,/, mice with [1- 14C]22:6n-3 using steady-state kinetic modeling. In addition, because Snca modulates 20:4n-6-CoA formation, we assessed microsomal Acsl activity using 22:6n-3 as a substrate. Although Snca gene ablation does not affect brain 22:6n-3 uptake, brain 22:6n-3-CoA mass was elevated 1.5-fold in the absence of Snca. This is consistent with the 1.6- to 2.2-fold increase in the incorporation rate and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 ± 0.5 ,mol/L, it did not bind 22:6n-3-CoA. These effects of Snca gene deletion on 22:6n-3 brain metabolism are opposite to what we reported previously for brain 20:4n-6 metabolism and are likely compensatory for the decreased 20:4n-6 metabolism in brains of Snca,/, mice. [source] Glucose metabolism and proliferation in glia: role of astrocytic gap junctionsJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Arantxa Tabernero Abstract Astrocytes play a well-established role in brain metabolism, being a key element in the capture of energetic compounds from the circulation and in their delivery to active neurons. Their metabolic status is affected in many pathological situations, such as gliomas, which are the most common brain tumors. This proliferative dysfunction is associated with changes in gap junctional communication, a property strongly developed in normal astrocytes studied both in vitro and in vivo. Here, we summarize and discuss the findings that have lead to the identification of a link between gap junctions, glucose uptake, and proliferation. Indeed, the inhibition of gap junctional communication is associated with an increase in glucose uptake due to a rapid change in the localization of both GLUT-1 and type I hexokinase. This effect persists due to the up-regulation of GLUT-1 and type I hexokinase and to the induction of GLUT-3 and type II hexokinase. In addition, cyclins D1 and D3 have been found to act as sensors of the inhibition of gap junctions and have been proposed to play the role of mediators in the mitogenic effect observed. Conversely, in C6 glioma cells, characterized by a low level of intercellular communication, an increase in gap junctional communication reduces glucose uptake by releasing type I and type II hexokinases from the mitochondria and decreases the exacerbated rate of proliferation due to the up-regulation of the Cdk inhibitors p21 and p27. Identification of the molecular actors involved in these pathways should allow the determination of potential therapeutic targets that could lead to the testing of alternative strategies to prevent, or at least slow down, the proliferation of glioma cells. [source] Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD geneJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2001Sankar Surendran Abstract Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a ,5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency. J. Neurosci. Res. 65:591,594, 2001. © 2001 Wiley-Liss, Inc. [source] Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: Implications for disease pathologyMOVEMENT DISORDERS, Issue 6 2004Elan D. Louis MD Abstract The pathological basis for essential tremor (ET) is not known; however, metabolic changes in the cerebellum can be observed in positron emission tomography (PET) and 1H magnetic resonance spectroscopic imaging (MRSI) studies. Tremor is relatively symmetric in ET, suggesting that underlying metabolic changes could be also symmetric. The degree of metabolic asymmetry in the cerebellum, however, has not yet been studied in ET, and knowledge about distribution and laterality of metabolic changes might shed some light on basic disease mechanisms. We measured brain metabolism (N -acetylaspartate[NAA]/creatine [tCR]) to obtain an asymmetry index for cerebellar cortical metabolism ET patients compared with that in controls. This index, a percentage, was calculated as |(value right , value left)|/(value right + value left) × 100. Multislice 1H MRSI data were acquired for 20 patients and 11 controls. In ET patients, mean right and left cerebellar cortical NAA/tCR values were 1.61 ± 0.42 and 1.55 ± 0.38, respectively, compared with 1.81 ± 0.62 and 1.87 ± 0.49 in controls. The difference between right and left cerebellar cortical NAA/tCR was also calculated for each subject. In ET patients, the mean right-left difference was 0.14 ± 0.11, compared with 0.32 ± 0.27 in controls (P = 0.016). The mean cerebellar cortical asymmetry index was low in ET (8.8 ± 6.1%), one-half of that in controls (17.0 ± 13.7%, P = 0.027). These data suggest that pathological lesions in ET patients, which remain elusive, might be distributed similarly in each cerebellar cortex. Postmortem studies are needed to confirm these preliminary imaging results. © 2004 Movement Disorder Society [source] Reflections on the application of 13C-MRS to research on brain metabolismNMR IN BIOMEDICINE, Issue 6-7 2003Peter Morris Abstract The power of 13C-MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Examples from animal studies, by examination of tissue extracts from the whole brain, brain slices and cultured cells, include observation of intermediates such as citrate and triose phosphates which have yielded novel information on neuronal/glial relationships. The use of 13C-labelled acetate as a specific precursor for glial metabolism provided evidence in support of the view that some of the GABA produced in the brain is derived from glial glutamine. Such studies have also provided direct evidence on the contribution of anaplerotic pathways to intermediary metabolism. Analogous studies are now being performed on the human brain, where 13C-acetate is used to quantitate the overall contribution of glial cells to intermediary metabolism, and use of 13C-glucose enables direct calculation of rates of flux through the TCA (FTCA) and of the glutamate,glutamine cycle (FCYC), leading to the conclusion that the rate of glial recycling of glutamate accounts for some 50% of FTCA. The rate of 0.74,,mol,min,1,g,1 for FTCA is compatible with PET rates of CMRglc of 0.3,0.4,,mol,min,1,g,1 (since each glucose molecule yields two molecules of pyruvate entering the TCA). Our brain activation studies showed a 60% increase in FTCA, which is very similar to the increases in CBF and in CMRglc observed in PET activation studies. Copyright © 2003 John Wiley & Sons, Ltd. [source] Shedding new light on brain metabolism and glial functionTHE JOURNAL OF PHYSIOLOGY, Issue 2 2002Denis Burdakov No abstract is available for this article. [source] Effect of chorioamnionitis on brain development and injury in premature newborns,ANNALS OF NEUROLOGY, Issue 2 2009Vann Chau MD Objective The association of chorioamnionitis and noncystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced magnetic resonance imaging. Methods Ninety-two preterm newborns (24,32 weeks gestation) were studied at a median age of 31.9 weeks and again at 40.3 weeks gestation. Histopathological chorioamnionitis and white matter injury were scored using validated systems. Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on magnetic resonance spectroscopy, and microstructure (average diffusivity and fractional anisotropy) on diffusion tensor imaging were calculated from predefined brain regions. Results Thirty-one (34%) newborns were exposed to histopathological chorioamnionitis, and 26 (28%) had white matter injury. Histopathological chorioamnionitis was not associated with an increased risk of white matter injury (relative risk: 1.2; p = 0.6). Newborns with postnatal infections and hypotension requiring therapy were at higher risk of white matter injury (p < 0.03). Adjusting for gestational age at scan and regions of interest, histopathological chorioamnionitis did not significantly affect brain metabolic and microstructural development (p > 0.1). In contrast, white matter injury was associated with lower N-acetylaspartate/choline (,8.9%; p = 0.009) and lower white matter fractional anisotropy (,11.9%; p = 0.01). Interpretation Histopathological chorioamnionitis does not appear to be associated with an increased risk of white matter injury on magnetic resonance imaging or with abnormalities of brain development. In contrast, postnatal infections and hypotension are associated with an increased risk of white matter injury in the premature newborn. Ann Neurol 2009;66:155,164 [source] Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia,CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 4 2004R. A. van Hulst Summary Objective:, Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. Design and setting:, Prospective animal study in a university laboratory. Subjects:, Eight adult Landrace/Yorkshire pigs. Interventions:, The microdialysis probe was inserted in the brain along with a multiparameter sensor and intracranial pressure (ICP) probe. The animals were ventilated in a pressure-controlled mode according to the open lung concept with an inspired oxygen fraction of 0·4/1·0. Starting at normoventilation (PaCO2 ±40 mmHg) two steps of both hypercapnia (PCO2 ± 70 and 100 mmHg) and hypocapnia (PaCO2 ± 20 and 30 mmHg) were performed. Under these conditions, brain glucose and lactate levels as well as brain oxygen (PbrO2), brain carbon dioxide (PbrCO2), brain pH (brpH), brain temperature and ICP were measured. Results:, At hypercapnia (PaCO2 = 102·7 mmHg) there were no significant changes in brain glucose and lactate but there was a significant increase in PbrCO2, PbrO2 and ICP. In contrast, at hypocapnia (PCO2 = 19·8 mmHg) there was a significant increase in brain lactate and a significant decrease in both brain glucose and PbrCO2. Conclusions:, Hypocapnia decreases brain glucose and increases brain lactate concentration, indicating anaerobic metabolism, whereas hypercapnia has no influence on levels of brain glucose and brain lactate. [source] Do psychotherapies produce neurobiological effects?ACTA NEUROPSYCHIATRICA, Issue 2 2006Veena Kumari Background:, An area of recent interest in psychiatric research is the application of neuroimaging techniques to investigate neural events associated with the development and the treatment of symptoms in a number of psychiatric disorders. Objective:, To examine whether psychological therapies modulate brain activity and, if so, to examine whether these changes similar to those found with relevant pharmacotherapy in various mental disorders. Methods:, Relevant data were identified from Pubmed and PsycInfo searches up to July 2005 using combinations of keywords including ,psychological therapy', ,behaviour therapy', ,depression', ,panic disorder', ,phobia', ,obsessive compulsive disorder', ,schizophrenia', ,psychosis', ,brain activity', ,brain metabolism', ,PET', ,SPECT' and ,fMRI'. Results:, There was ample evidence to demonstrate that psychological therapies produce changes at the neural level. The data, for example in depression, panic disorder, phobia and obsessive compulsive disorder (OCD), clearly suggested that a change in patients' symptoms and maladaptive behaviour at the mind level with psychological techniques is accompanied with functional brain changes in relevant brain circuits. In many studies, cognitive therapies and drug therapies achieved therapeutic gains through the same neural pathways although the two forms of treatment may still have different mechanisms of action. Conclusions:, Empirical research indicates a close association between the ,mind' and the ,brain' in showing that changes made at the mind level in a psychotherapeutic context produce changes at the brain level. The investigation of changes in neural activity with psychological therapies is a novel area which is likely to enhance our understanding of the mechanisms for therapeutic changes across a range of disorders. [source] | |||||||||||||||||||||||||