WorldWideScience

Sample records for brain glucose content

  1. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  2. Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: a localized 13C NMR study

    OpenAIRE

    Lei, Hongxia; Gruetter, Rolf

    2006-01-01

    While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 4...

  3. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

    This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

  4. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  5. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  6. Impaired brain energy gain upon a glucose load in obesity.

    Science.gov (United States)

    Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

    2018-03-06

    There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

  7. Revisiting Glycogen Content in the Human Brain.

    Science.gov (United States)

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

    2015-12-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.

  8. Glucose transport in brain - effect of inflammation.

    Science.gov (United States)

    Jurcovicova, J

    2014-01-01

    Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

  9. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  10. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  11. Evidence for brain glucose dysregulation in Alzheimer's disease.

    Science.gov (United States)

    An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

    2018-03-01

    It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  12. Sensing of glucose in the brain.

    Science.gov (United States)

    Thorens, Bernard

    2012-01-01

    The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

  13. Linking neuronal brain activity to the glucose metabolism.

    Science.gov (United States)

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  14. [Glucose homeostasis and gut-brain connection].

    Science.gov (United States)

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  15. Ketosis proportionately spares glucose utilization in brain.

    Science.gov (United States)

    Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

    2013-08-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

  16. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  17. Brain areas and pathways in the regulation of glucose metabolism

    NARCIS (Netherlands)

    Diepenbroek, Charlene; Serlie, Mireille J.; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E.

    2013-01-01

    Glucose is the most important source of fuel for the brain and its concentration must be kept within strict boundaries to ensure the organism's optimal fitness. To maintain glucose homeostasis, an optimal balance between glucose uptake and glucose output is required. Besides managing acute changes

  18. Regional brain glucose use in unstressed rats after two days of starvation

    International Nuclear Information System (INIS)

    Mans, A.M.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

  19. Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.

    Science.gov (United States)

    Kiyatkin, Eugene A; Wakabayashi, Ken T

    2015-01-21

    Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.

  20. Incorporation of 14C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

    International Nuclear Information System (INIS)

    Sikorska, M.; Gorzkowski, B.; Szumanska, G.; Smialek, M.

    1975-01-01

    Incorporation of 14 C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value. (Z.M.)

  1. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    Science.gov (United States)

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  3. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    OpenAIRE

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s dis...

  4. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between...

  5. Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

    DEFF Research Database (Denmark)

    Gejl, Michael; Egefjord, Lærke; Lerche, Susanne

    2012-01-01

    Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD...... in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia....

  6. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...

  7. Cooperation between brain and islet in glucose homeostasis and diabetes

    Science.gov (United States)

    Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

    2014-01-01

    Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

  8. Influence of ketamine on regional brain glucose use

    International Nuclear Information System (INIS)

    Davis, D.W.; Mans, A.M.; Biebuyck, J.F.; Hawkins, R.A.

    1988-01-01

    The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with [6- 14 C]glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic, steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus

  9. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Science.gov (United States)

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  10. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    Science.gov (United States)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury

    OpenAIRE

    Meierhans, Roman; B?chir, Markus; Ludwig, Silke; Sommerfeld, Jutta; Brandi, Giovanna; Haberth?r, Christoph; Stocker, Reto; Stover, John F

    2010-01-01

    Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 ?l/min, collecting samples at 60 minute intervals. Occult metabolic alteratio...

  12. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose beneath 1 mM in patients with severe traumatic brain injury.

    OpenAIRE

    Meierhans, R; Bechir, M; Ludwig, S; Sommerfeld, J; Brandi, G; Haberthur, C; Stocker, R; Stover, J F

    2010-01-01

    ABSTRACT: INTRODUCTION: The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 mul/ min, collecting samples at 60 minute intervals. Occult metab...

  13. Epigenetic regulation of the glucose transporter gene Slc2a1 by β-hydroxybutyrate underlies preferential glucose supply to the brain of fasted mice.

    Science.gov (United States)

    Tanegashima, Kosuke; Sato-Miyata, Yukiko; Funakoshi, Masabumi; Nishito, Yasumasa; Aigaki, Toshiro; Hara, Takahiko

    2017-01-01

    We carried out liquid chromatography-tandem mass spectrometry analysis of metabolites in mice. Those metabolome data showed that hepatic glucose content is reduced, but that brain glucose content is unaffected, during fasting, consistent with the priority given to brain glucose consumption during fasting. The molecular mechanisms for this preferential glucose supply to the brain are not fully understood. We also showed that the fasting-induced production of the ketone body β-hydroxybutyrate (β-OHB) enhances expression of the glucose transporter gene Slc2a1 (Glut1) via histone modification. Upon β-OHB treatment, Slc2a1 expression was up-regulated, with a concomitant increase in H3K9 acetylation at the critical cis-regulatory region of the Slc2a1 gene in brain microvascular endothelial cells and NB2a neuronal cells, shown by quantitative PCR analysis and chromatin immunoprecipitation assay. CRISPR/Cas9-mediated disruption of the Hdac2 gene increased Slc2a1 expression, suggesting that it is one of the responsible histone deacetylases (HDACs). These results confirm that β-OHB is a HDAC inhibitor and show that β-OHB plays an important role in fasting-induced epigenetic activation of a glucose transporter gene in the brain. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  14. High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature.

    Science.gov (United States)

    Li, Wei; Maloney, Ronald E; Aw, Tak Yee

    2015-08-01

    We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature

    Directory of Open Access Journals (Sweden)

    Wei Li

    2015-08-01

    Full Text Available We previously demonstrated that in normal glucose (5 mM, methylglyoxal (MG, a model of carbonyl stress induced brain microvascular endothelial cell (IHEC dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC. Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia; moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation. Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG–occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG–occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.

  16. Glucose metabolism, diet composition, and the brain

    NARCIS (Netherlands)

    Diepenbroek, C.

    2017-01-01

    Excessive intake of saturated fat and sugar contributes to both obesity and diabetes development. Since intake of fat and sugar-sweetened beverages exceeds recommended levels worldwide, it is essential to: 1) Understand how fat and sugar intake affect glucose metabolism, and 2) Expand the knowledge

  17. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    Science.gov (United States)

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  18. Gut-Brain Glucose Signaling in Energy Homeostasis.

    Science.gov (United States)

    Soty, Maud; Gautier-Stein, Amandine; Rajas, Fabienne; Mithieux, Gilles

    2017-06-06

    Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits. It also leads to questions on the advantage conferred by its conservation through a process of natural selection. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  20. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  1. Effects of MDMA on blood glucose levels and brain glucose metabolism

    International Nuclear Information System (INIS)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M.; Arango, C.; Ricaurte, G.

    2007-01-01

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  2. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    Science.gov (United States)

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-05-01

    Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Glucose transporter of the human brain and blood-brain barrier

    International Nuclear Information System (INIS)

    Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

    1988-01-01

    We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

  4. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    OpenAIRE

    Gejl, Michael; Lerche, Susanne; Egefjord, L?rke; Brock, Birgitte; M?ller, Niels; Vang, Kim; Rodell, Anders B.; Bibby, Bo M.; Holst, Jens J.; Rungby, J?rgen; Gjedde, Albert

    2013-01-01

    In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose concentration together with increased net blood-brain clearance and brain metabolism, but it is not known whether this effect depends on the prevailing plasma glucose (PG) concentration. In hypoglycemia, glucose depletion potentially impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the effect of hypoglycemia. To test the hypothesis, we determined glucose transport and consumption rates in seven h...

  5. The Alzheimer's Disease-Related Glucose Metabolic Brain Pattern

    NARCIS (Netherlands)

    Teune, Laura K.; Strijkert, Fijanne; Renken, Remco J.; Izaks, Gerbrand J.; de Vries, Jeroen J.; Segbers, Marcel; Roerdink, Jos B. T. M.; Dierckx, Rudi A. J. O.; Leenders, Klaus L.

    2014-01-01

    Purpose: [F-18] fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile

  6. Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

    DEFF Research Database (Denmark)

    Lerche, Susanne; Brock, Birgitte; Rungby, Jørgen

    2008-01-01

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested......-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitary-pancreatic normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer. RESULTS: On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P = 0...... that a hormone involved in postprandial glucose regulation also limits glucose delivery to brain tissue and hence provides a possible regulatory mechanism for the link between plasma glucose and brain glucose. Because GLP-1 reduces glucose uptake across the intact blood-brain barrier at normal glycemia, GLP-1...

  7. Brain glucose metabolism in an animal model of depression.

    Science.gov (United States)

    Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

    2015-06-04

    An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

  8. Brain glucose sensing in homeostatic and hedonic regulation.

    Science.gov (United States)

    Steinbusch, Laura; Labouèbe, Gwenaël; Thorens, Bernard

    2015-09-01

    Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  10. Simultaneous measurement of glucose transport and utilization in the human brain

    OpenAIRE

    Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.; Öz, Gülin

    2011-01-01

    Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose tra...

  11. Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

    International Nuclear Information System (INIS)

    Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

    1991-01-01

    The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

  12. Steady-state cerebral glucose concentrations and transport in the human brain

    OpenAIRE

    Gruetter, R.; Ugurbil, K.; Seaquist, E. R.

    1998-01-01

    Understanding the mechanism of brain glucose transport across the blood- brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport nave been generally described using standard Michaelis-Menten kinetics. These models predict that the steady- state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, K(t). In experiments wh...

  13. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    Science.gov (United States)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  14. Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

    Science.gov (United States)

    Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

    2015-07-01

    Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (Pbrain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

  15. Effect of beverage glucose and sodium content on fluid delivery

    Directory of Open Access Journals (Sweden)

    Cole Johnny

    2009-02-01

    Full Text Available Abstract Background Rapid fluid delivery from ingested beverages is the goal of oral rehydration solutions (ORS and sports drinks. Objective The aim of the present study was to investigate the effects of increasing carbohydrate and sodium content upon fluid delivery using a deuterium oxide (D2O tracer. Design Twenty healthy male subjects were divided into two groups of 10, the first group was a carbohydrate group (CHO and the second a sodium group (Na. The CHO group ingested four different drinks with a stepped increase of 3% glucose from 0% to 9% while sodium concentration was 20 mmol/L. The Na group ingested four drinks with a stepped increase of 20 mmol/L from 0 mmol/L to 60 mmol/l while glucose concentration was 6%. All beverages contained 3 g of D2O. Subjects remained seated for two hours after ingestion of the experimental beverage, with blood taken every 5 min in the first hour and every 10 min in the second hour. Results Including 3% glucose in the beverage led to a significantly greater AUC 60 min (19640 ± 1252 δ‰ vs. VSMOW.60 min than all trials. No carbohydrate (18381 ± 1198 δ‰ vs. VSMOW.60 min had a greater AUC 60 min than a 6% (16088 ± 1359 δ‰ vs. VSMOW.60 min and 9% beverage (13134 ± 1115 δ‰ vs. VSMOW.60 min; the 6% beverage had a significantly greater AUC 60 min than the 9% beverage. There was no difference in fluid delivery between the different sodium beverages. Conclusion In conclusion the present study showed that when carbohydrate concentration in an ingested beverage was increased above 6% fluid delivery was compromised. However, increasing the amount of sodium (0–60 mmol/L in a 6% glucose beverage did not lead to increases in fluid delivery.

  16. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    Science.gov (United States)

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  17. Effect of glucose level on brain FDG-PET images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Young; Lee, Yong Ki; Ahn, Sung Min [Dept. of Radiological Science, Gachon University, Seongnam (Korea, Republic of)

    2017-06-15

    In addition to tumors, normal tissues, such as the brain and myocardium can intake {sup 18}F-FDG, and the amount of {sup 18}F-FDG intake by normal tissues can be altered by the surrounding environment. Therefore, a process is necessary during which the contrasts of the tumor and normal tissues can be enhanced. Thus, this study examines the effects of glucose levels on FDG PET images of brain tissues, which features high glucose activity at all times, in small animals. Micro PET scan was performed on fourteen mice after injecting {sup 18}F-FDG. The images were compared in relation to fasting. The findings showed that the mean SUV value w as 0 .84 higher in fasted mice than in non-fasted mice. During observation, the images from non-fasted mice showed high accumulation in organs other than the brain with increased surrounding noise. In addition, compared to the non-fasted mice, the fasted mice showed higher early intake and curve increase. The findings of this study suggest that fasting is important in assessing brain functions in brain PET using {sup 18}F-FDG. Additional studies to investigate whether caffeine levels and other preprocessing items have an impact on the acquired images would contribute to reducing radiation exposure in patients.

  18. Effect of glucose level on brain FDG-PET images

    International Nuclear Information System (INIS)

    Kim, In Young; Lee, Yong Ki; Ahn, Sung Min

    2017-01-01

    In addition to tumors, normal tissues, such as the brain and myocardium can intake 18 F-FDG, and the amount of 18 F-FDG intake by normal tissues can be altered by the surrounding environment. Therefore, a process is necessary during which the contrasts of the tumor and normal tissues can be enhanced. Thus, this study examines the effects of glucose levels on FDG PET images of brain tissues, which features high glucose activity at all times, in small animals. Micro PET scan was performed on fourteen mice after injecting 18 F-FDG. The images were compared in relation to fasting. The findings showed that the mean SUV value w as 0 .84 higher in fasted mice than in non-fasted mice. During observation, the images from non-fasted mice showed high accumulation in organs other than the brain with increased surrounding noise. In addition, compared to the non-fasted mice, the fasted mice showed higher early intake and curve increase. The findings of this study suggest that fasting is important in assessing brain functions in brain PET using 18 F-FDG. Additional studies to investigate whether caffeine levels and other preprocessing items have an impact on the acquired images would contribute to reducing radiation exposure in patients

  19. Mechanisms and significance of brain glucose signaling in energy balance, glucose homeostasis, and food-induced reward.

    Science.gov (United States)

    Devarakonda, Kavya; Mobbs, Charles V

    2016-12-15

    The concept that hypothalamic glucose signaling plays an important role in regulating energy balance, e.g., as instantiated in the so-called "glucostat" hypothesis, is one of the oldest in the field of metabolism. However the mechanisms by which neurons in the hypothalamus sense glucose, and the function of glucose signaling in the brain, has been difficult to establish. Nevertheless recent studies probing mechanisms of glucose signaling have also strongly supported a role for glucose signaling in regulating energy balance, glucose homeostasis, and food-induced reward. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Sikorska, M; Gorzkowski, B; Szumanska, G; Smialek, M [Polska Akademia Nauk, Warsaw. Centrum Medycyny Doswiadczalnej i Klinicznej; Panstwowy Zaklad Higieny, Warsaw (Poland))

    1975-01-01

    Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value.

  1. Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.

    Science.gov (United States)

    Wakabayashi, Ken T; Spekterman, Laurence; Kiyatkin, Eugene A

    2016-06-01

    Glucose, a primary metabolic substrate for cellular activity, must be delivered to the brain for normal neural functions. Glucose is also a unique reinforcer; in addition to its rewarding sensory properties and metabolic effects, which all natural sugars have, glucose crosses the blood-brain barrier and acts on glucoreceptors expressed on multiple brain cells. To clarify the role of this direct glucose action in the brain, we compared the neural and behavioural effects of glucose with those induced by fructose, a sweeter yet metabolically equivalent sugar. First, by using enzyme-based biosensors in freely moving rats, we confirmed that glucose rapidly increased in the nucleus accumbens in a dose-dependent manner after its intravenous delivery. In contrast, fructose induced a minimal response only after a large-dose injection. Second, we showed that naive rats during unrestricted access consumed larger volumes of glucose than fructose solution; the difference appeared with a definite latency during the initial exposure and strongly increased during subsequent tests. When rats with equal sugar experience were presented with either glucose or fructose in alternating order, the consumption of both substances was initially equal, but only the consumption of glucose increased during subsequent sessions. Finally, rats with equal glucose-fructose experience developed a strong preference for glucose over fructose during a two-bottle choice procedure; the effect appeared with a definite latency during the initial test and greatly amplified during subsequent tests. Our results suggest that direct entry of glucose in the brain and its subsequent effects on brain cells could be critical for the experience-dependent escalation of glucose consumption and the development of glucose preference over fructose. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  2. Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Murrin L Charles

    2011-03-01

    Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

  3. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    Science.gov (United States)

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

  4. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  5. Metabolism of glucose in brain of patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki.

    1984-01-01

    We examined 11 C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11 C-glucose (per os). 11 C-glucose was prepared from 11 CO 2 by photosynthesis. 1) No significant difference was observed in the 11 C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11 C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

  6. A brain-liver circuit regulates glucose homeostasis.

    Science.gov (United States)

    Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

    2005-01-01

    Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

  7. Effects of lithium on brain glucose metabolism in healthy men.

    Science.gov (United States)

    Kohno, Tomoya; Shiga, Tohru; Toyomaki, Atsuhito; Kusumi, Ichiro; Matsuyama, Tetsuaki; Inoue, Tetsuya; Katoh, Chietsugu; Koyama, Tsukasa; Tamaki, Nagara

    2007-12-01

    Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 +/- 6 years) underwent positron emission tomographic scans with F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.

  8. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

    NARCIS (Netherlands)

    van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

    2005-01-01

    OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

  9. Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

    Science.gov (United States)

    Patet, Camille; Quintard, Hervé; Suys, Tamarah; Bloch, Jocelyne; Daniel, Roy T; Pellerin, Luc; Magistretti, Pierre J; Oddo, Mauro

    2015-10-15

    Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r = 0.56; p 25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

  10. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    DEFF Research Database (Denmark)

    Gejl, Michael; Lerche, Susanne; Egefjord, Lærke

    2013-01-01

    phosphorylation velocity (V max) in the gray matter regions of cerebral cortex, thalamus, and cerebellum, as well as increased blood-brain glucose transport capacity (T max) in gray matter, white matter, cortex, thalamus, and cerebellum. In hypoglycemia, GLP-1 had no effects on net glucose metabolism, brain...

  11. Simultaneous measurement of glucose transport and utilization in the human brain

    Science.gov (United States)

    Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

    2011-01-01

    Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

  12. Regional differences in brain glucose metabolism determined by imaging mass spectrometry

    OpenAIRE

    André Kleinridders; Heather A. Ferris; Michelle L. Reyzer; Michaela Rath; Marion Soto; M. Lisa Manier; Jeffrey Spraggins; Zhihong Yang; Robert C. Stanton; Richard M. Caprioli; C. Ronald Kahn

    2018-01-01

    Objective: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Metho...

  13. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Science.gov (United States)

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  14. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

    Science.gov (United States)

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-03-11

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

  15. Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.

    Science.gov (United States)

    Patching, Simon G

    2017-03-01

    Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.

  16. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  17. GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish.

    Science.gov (United States)

    Marín-Juez, Rubén; Rovira, Mireia; Crespo, Diego; van der Vaart, Michiel; Spaink, Herman P; Planas, Josep V

    2015-01-01

    Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.

  18. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    Science.gov (United States)

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  19. Effect of test meals of varying dietary fiber content on plasma insulin and glucose response.

    Science.gov (United States)

    Potter, J G; Coffman, K P; Reid, R L; Krall, J M; Albrink, M J

    1981-03-01

    To assess the effect of dietary fiber on glucose tolerance four different meals of varying fiber content but identical protein fat and carbohydrate content were fed to eight healthy men aged 22 to 45. Each meal provided 75 g of carbohydrate as liquid glucose formula, as brown rice, pinto beans, or All Bran. The mean plasma glucose and insulin responses were highest following the formula, and least for All Bran and pinto beans. Rice produced nearly as great a rise in insulin and glucose as did the formula. The rank of each meal by content of neutral detergent fiber was nearly the inverse of the rank by magnitude of the insulin response evoked, fiber content being greatest in All Bran (18 g) and pinto beans (16.2 g), low in rice (2.8 g) and absent from the formula. It was concluded that dietary fiber dampened the insulin response to a high carbohydrate meal.

  20. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    Science.gov (United States)

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  1. Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia

    NARCIS (Netherlands)

    van Hulst, R. A.; Lameris, T. W.; Haitsma, J. J.; Klein, J.; Lachmann, B.

    2004-01-01

    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

  2. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was

  3. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

    NARCIS (Netherlands)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W.; Pfluger, Paul T.; Fernandez, Ana M.; Luquet, Serge; Woods, Stephen C.; Torres-Alemán, Ignacio; Kahn, C. Ronald; Götz, Magdalena; Horvath, Tamas L.; Tschöp, Matthias H.

    2016-01-01

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and

  4. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

    Science.gov (United States)

    Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

    2017-03-01

    GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.

  5. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation

    Science.gov (United States)

    Reno, Candace M.; Puente, Erwin C.; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.

    2017-01-01

    GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. PMID:27797912

  6. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  7. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

    Science.gov (United States)

    Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

    2016-02-01

    Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

  8. In vivo measurements of brain glucose transport using the reversible michaelis-menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia

    OpenAIRE

    Choi, I.-Y.; Lee, S.-P.; Kim, S.-G.; Gruetter, R.

    2001-01-01

    Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma ...

  9. Fine print in isotope effects: the glucose anomeric equilibrium and binding of glucose to human brain hexokinase

    International Nuclear Information System (INIS)

    Lewis, B.E; Schramm, V.L.

    2002-01-01

    Binding isotope effects are a sensitive measure of changes in molecular vibrational character that occur during ligand-receptor binding. In this study, we have measured isotope effects on the binding of glucose to human brain hexokinase using the ultrafiltration method, with the following results: 0.991±0.001, 0.908±0.003, 1.010±0.001, 0.974±0.002, 1.022±0.002 for [ 14 C]-glucose mixed with [1- 3 H]-, [2- 3 H]-, [3- 3 H]-, [5- 3 H]-, [6,6- 3 H]-glucose, respectively. Comparing the observed data with isotope effects on the anomeric equilibrium in glucose reported previously proves the existence of binding isotope effects in this system. Preliminary computational results are presented to explain the observed binding isotope effects in terms of hydrogen bond patterns and molecular crowding found in the binary complex of sugar and enzyme. (author)

  10. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    International Nuclear Information System (INIS)

    Redies, C.; Hoffer, L.J.; Beil, C.

    1989-01-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

  11. Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

    Science.gov (United States)

    Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

    2014-03-01

    Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

  12. Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

    Science.gov (United States)

    Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

    2016-07-01

    Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    Science.gov (United States)

    2007-03-30

    Tymoczko et al. 2002). Both cardiac muscle and brain contain the necessary enzymes to metabolize either glucose or ketone bodies . The enzymes... metabolic phenotype of astrocytes and neurons in vitro; and to determine whether antipsychotic drug administration affects glucose metabolites in...Cortical Astrocytes and Neurons 20 Abstract 21 v Introduction ~ 22 Results 24 Enriched Astrocyte and Neuronal Cultures Display Unique Metabolic

  14. Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

    Science.gov (United States)

    Jahagirdar, V; McNay, EC

    2012-01-01

    Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often encountered in combination with metabolic disorders, such as diabetes, and may cause additional metabolic dysregulation and hence worsening of disease states. TH’s potential as a regulator of brain glucose metabolism is heightened by interactions with insulin signaling, but there have been relatively few studies on this topic or on the actions of TH in a mature brain. This review discusses evidence for mechanistic links between TH, insulin, cognitive function, and brain glucose metabolism, and suggests that TH is a good candidate to be a modulator of memory processes, likely at least in part by modulation of central insulin signaling and glucose metabolism. PMID:22437199

  15. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  16. Body Fat Content, Distribution and Blood Glucose Concentration ...

    African Journals Online (AJOL)

    disease and 2% are due to Diabetes mellitus, 9% ... study was to examine the relationship between body fat content, ..... A meta-analysis of prospective studies. ... A.A.1., Esterhuizen, T., Gouws, E.,. Pirie, F.J., Omar, M.A. (2008). Diabetes.

  17. Mapping glucose-mediated gut-to-brain signalling pathways in humans.

    Science.gov (United States)

    Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T

    2014-08-01

    Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.

  18. Mapping glucose-mediated gut-to-brain signalling pathways in humans☆

    Science.gov (United States)

    Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.

    2014-01-01

    Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436

  19. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

    Science.gov (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

    2017-06-01

    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  20. Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    WANG Qiong; LI Ai-lin; ZHI Da-shi; HUANG Hui-ling

    2007-01-01

    Objective:To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.Methods: Thirty-one patients with STBI ( GCS ≤8) were randomly divided into hypothermic group (Group A) and control group (Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.Results: In comparison with the control group, lactate/glucose ratio ( L/G) , lactate/pyruvate ratio ( L/P) and glycerol (Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.Conclusions: Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

  1. Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Jakobsen, J.; Nedergaard, M.; Aarslew-Jensen, M.; Diemer, N.H.

    1990-01-01

    Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [ 3 H]-2-deoxy-D-glucose and [ 14 C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work

  2. Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes.

    Science.gov (United States)

    Bell, J E; Hume, R; Busuttil, A; Burchell, A

    1993-10-01

    Using an antibody raised against the catalytic subunit of glucose-6-phosphatase, this enzyme was immunolocalized in many astrocytes in 20 normal human brains. Double immunofluorescence studies showed co-localization of glial fibrillary acidic protein (GFAP) with glucose-6-phosphatase in astrocytes. However, not all GFAP-positive cells were also glucose-6-phosphatase positive, indicating that some astrocytes do not contain demonstrable expression of this enzyme. Reactive astrocytes in a variety of abnormal brains were strongly glucose-6-phosphatase positive, but neoplastic astrocytes were often only weakly positive. Expression of the enzyme could not be demonstrated in radial glia, neurons or oligodendroglia. Astrocytes normally contain glycogen and the demonstration that some astrocytes also contain glucose-6-phosphatase indicates that they are competent for both glycogenolysis and gluconeogenesis, which may be critical for neuronal welfare.

  3. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    Science.gov (United States)

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-05

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Science.gov (United States)

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  5. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  6. Glucose metabolism and astrocyte-neuron interactions in the neonatal brain.

    Science.gov (United States)

    Brekke, Eva; Morken, Tora Sund; Sonnewald, Ursula

    2015-03-01

    Glucose is essentially the sole fuel for the adult brain and the mapping of its metabolism has been extensive in the adult but not in the neonatal brain, which is believed to rely mainly on ketone bodies for energy supply. However, glucose is absolutely indispensable for normal development and recent studies have shed light on glycolysis, the pentose phosphate pathway and metabolic interactions between astrocytes and neurons in the 7-day-old rat brain. Appropriately (13)C labeled glucose was used to distinguish between glycolysis and the pentose phosphate pathway during development. Experiments using (13)C labeled acetate provided insight into the GABA-glutamate-glutamine cycle between astrocytes and neurons. It could be shown that in the neonatal brain the part of this cycle that transfers glutamine from astrocytes to neurons is operating efficiently while, in contrast, little glutamate is shuttled from neurons to astrocytes. This lack of glutamate for glutamine synthesis is compensated for by anaplerosis via increased pyruvate carboxylation relative to that in the adult brain. Furthermore, compared to adults, relatively more glucose is prioritized to the pentose phosphate pathway than glycolysis and pyruvate dehydrogenase activity. The reported developmental differences in glucose metabolism and neurotransmitter synthesis may determine the ability of the brain at various ages to resist excitotoxic insults such as hypoxia-ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

    Science.gov (United States)

    Akman, Cigdem Inan; Provenzano, Frank; Wang, Dong; Engelstad, Kristin; Hinton, Veronica; Yu, Julia; Tikofsky, Ronald; Ichese, Masonari; De Vivo, Darryl C

    2015-02-01

    (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy. Copyright © 2014. Published by Elsevier B.V.

  9. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  10. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    International Nuclear Information System (INIS)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-01-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  11. Visible micro-Raman spectroscopy for determining glucose content in beverage industry.

    Science.gov (United States)

    Delfino, I; Camerlingo, C; Portaccio, M; Ventura, B Della; Mita, L; Mita, D G; Lepore, M

    2011-07-15

    The potential of Raman spectroscopy with excitation in the visible as a tool for quantitative determination of single components in food industry products was investigated by focusing the attention on glucose content in commercial sport drinks. At this aim, micro-Raman spectra in the 600-1600cm(-1) wavenumber shift region of four sport drinks were recorded, showing well defined and separated vibrational fingerprints of the various contained sugars (glucose, fructose and sucrose). By profiting of the spectral separation of some peculiar peaks, glucose content was quantified by using a multivariate statistical analysis based on the interval Partial Least Square (iPLS) approach. The iPLS model needed for data analysis procedure was built by using glucose aqueous solutions at known sugar concentrations as calibration data. This model was then applied to sport drink spectra and gave predicted glucose concentrations in good agreement with the values obtained by using a biochemical assay. These results represent a significant step towards the development of a fast and simple method for the on-line glucose quantification in products of food and beverage industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2018-03-01

    Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

  13. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  14. Relationship between regional brain glucose metabolism and temperament factor of personality

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

  15. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    Wong, K.L.; Tyce, G.M.

    1983-01-01

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  16. Effect of nitroimidazoles on glucose utilization and lactate accumulation in mouse brain

    International Nuclear Information System (INIS)

    Chao, C.F.; Subjeck, J.R.; Brody, H.; Shen, J.; Johnson, R.J.R.

    1984-01-01

    The radiation sensitizers misonidazole (MISO) and desmethylmisonidazole (DMM) can produce central and peripheral neuropathy in patients and laboratory animals. Nitroimidazoles can also interfere with glycolysis in vitro under aerobic and anaerobic conditions. In the present work, the authors studied the effect of MISO or DMM on lactate production and glucose utilization in mouse brain. It is observed that these compounds result in a 25% inhibition of lactate production in brain slices relative to the control at a 10 mM level. Additionally, MISO (1.0 mg/g/day) or DMM (1.4 mg/g/day) were administered daily (oral) for 1, 4, 7, or 14 days to examine the effect of these two drugs on the regional glucose utilization in C3Hf mouse brain. Five microcuries of 2-deoxy[ 14 C]glucose was given following the last drug dose and autoradiographs of serial brain sections were made and analyzed by a densitometer. Following a single dose of either MISO or DMM, no significant differences in glucose uptake were observed when compared with controls. However, following 4, 7, and 14 doses the rate of glucose utilization was significantly reduced in the intoxicated animals. Larger reductions were measured in specific regions including the posterior colliculus, cochlear nuclei, vestibular nuclei, and pons with increasing effects observed at later stages. These results share a degree of correspondence with the regional brain pathology produced by these nitroimidazoles

  17. Linking neuronal brain activity to the glucose metabolism

    OpenAIRE

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  18. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle.

    Science.gov (United States)

    Marette, A; Dimitrakoudis, D; Shi, Q; Rodgers, C D; Klip, A; Vranic, M

    1999-02-01

    We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.

  20. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

    Science.gov (United States)

    Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

    2014-06-01

    The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Initial investigation of glucose metabolism in mouse brain using enriched 17 O-glucose and dynamic 17 O-MRS.

    Science.gov (United States)

    Borowiak, Robert; Reichardt, Wilfried; Kurzhunov, Dmitry; Schuch, Christian; Leupold, Jochen; Krafft, Axel Joachim; Reisert, Marco; Lange, Thomas; Fischer, Elmar; Bock, Michael

    2017-08-01

    In this initial work, the in vivo degradation of 17 O-labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct 17 O-magnetic resonance spectroscopy (MRS) was used in the mouse brain at 9.4 T. Non-localized spectra were acquired with a custom-built transmit/receive (Tx/Rx) two-turn surface coil and a free induction decay (FID) sequence with a short TR of 5.4 ms. The dynamics of labeled oxygen in the anomeric 1-OH and 6-CH 2 OH groups was detected using a Hankel-Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time-resolved 17 O-MRS (temporal resolution, 42/10.5 s) was performed in 10 anesthetized (1.25% isoflurane) mice after injection of a 2.2 M solution containing 2.5 mg/g body weight of differently labeled 17 O-glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H 2 17 O concentration-time course, a mean apparent cerebral metabolic rate of 17 O-labeled glucose in mouse brain of CMR Glc  = 0.07 ± 0.02 μmol/g/min was extracted, which is of the same order of magnitude as a literature value of 0.26 ± 0.06 μmol/g/min reported by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of 17 O-labeled glucose at the C1 and C6 positions with dynamic 17 O-MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6- 17 OH label in the 6-CH 2 OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H 2 17 O, whereas C1- 17 OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic 17 O-MRS of highly labeled 17 O-glucose could provide a valuable non-radioactive alternative to FDG PET in order to investigate glucose metabolism. Copyright © 2017 John Wiley & Sons, Ltd.

  3. 13C NMR for the assessment of human brain glucose metabolism in vivo

    International Nuclear Information System (INIS)

    Beckman, N.; Seelig, J.; Turkalj, I.; Keller, U.

    1991-01-01

    Proton-decoupled 13 C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1- 13 C]glucose in normal volunteers. In addition to 13 C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1- 13 C]glucose, the signals of α- and β-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 minutes. The spatial localization of the different regions of interest was confirmed by 13 C NMR spectroscopic imaging with a time resolution of 9 minutes. Increasing the enrichment level to 99% [1- 13 C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1- 13 C]glucose. The time course of 13 C label incorporation into the C 2 , C 3 , and C 4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body

  4. Importance of the gut-brain axis in the control of glucose homeostasis.

    Science.gov (United States)

    Migrenne, Stéphanie; Marsollier, Nicolas; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2006-12-01

    Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.

  5. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    Science.gov (United States)

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

  6. Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

    Science.gov (United States)

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-01-01

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

  7. Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise.

    Directory of Open Access Journals (Sweden)

    Hsuan-Ying Chen

    Full Text Available Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p. 30 min before treadmill exercise (20 m/min for 60 min. Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P<0.05 in the Mg group. Lactate levels in the muscle, blood, and brain rapidly and significantly increased in both groups during exercise, and brain lactate levels in the Mg group further elevated (P<0.05 than those in the control group during exercise. Lactate levels significantly decreased after exercise in both groups. In conclusion, Mg enhanced glucose availability in the peripheral and central systems, and increased lactate clearance in the muscle during exercise.

  8. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  9. Glucose variability negatively impacts long-term functional outcome in patients with traumatic brain injury.

    Science.gov (United States)

    Matsushima, Kazuhide; Peng, Monica; Velasco, Carlos; Schaefer, Eric; Diaz-Arrastia, Ramon; Frankel, Heidi

    2012-04-01

    Significant glycemic excursions (so-called glucose variability) affect the outcome of generic critically ill patients but has not been well studied in patients with traumatic brain injury (TBI). The purpose of this study was to evaluate the impact of glucose variability on long-term functional outcome of patients with TBI. A noncomputerized tight glucose control protocol was used in our intensivist model surgical intensive care unit. The relationship between the glucose variability and long-term (a median of 6 months after injury) functional outcome defined by extended Glasgow Outcome Scale (GOSE) was analyzed using ordinal logistic regression models. Glucose variability was defined by SD and percentage of excursion (POE) from the preset range glucose level. A total of 109 patients with TBI under tight glucose control had long-term GOSE evaluated. In univariable analysis, there was a significant association between lower GOSE score and higher mean glucose, higher SD, POE more than 60, POE 80 to 150, and single episode of glucose less than 60 mg/dL but not POE 80 to 110. After adjusting for possible confounding variables in multivariable ordinal logistic regression models, higher SD, POE more than 60, POE 80 to 150, and single episode of glucose less than 60 mg/dL were significantly associated with lower GOSE score. Glucose variability was significantly associated with poorer long-term functional outcome in patients with TBI as measured by the GOSE score. Well-designed protocols to minimize glucose variability may be key in improving long-term functional outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  11. Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

    Science.gov (United States)

    Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

    2015-06-01

    We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

  12. T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

    Science.gov (United States)

    Paech, Daniel; Schuenke, Patrick; Koehler, Christina; Windschuh, Johannes; Mundiyanapurath, Sibu; Bickelhaupt, Sebastian; Bonekamp, David; Bäumer, Philipp; Bachert, Peter; Ladd, Mark E; Bendszus, Martin; Wick, Wolfgang; Unterberg, Andreas; Schlemmer, Heinz-Peter; Zaiss, Moritz; Radbruch, Alexander

    2017-12-01

    Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

  13. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    Science.gov (United States)

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  14. Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

    Science.gov (United States)

    Perneczky, R; Drzezga, A; Diehl-Schmid, J; Schmid, G; Wohlschläger, A; Kars, S; Grimmer, T; Wagenpfeil, S; Monsch, A; Kurz, A

    2006-09-01

    Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

  15. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  16. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

    Science.gov (United States)

    McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

    2015-09-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

    Science.gov (United States)

    McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

    2015-01-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

  18. Exercise, energy intake, glucose homeostasis, and the brain.

    Science.gov (United States)

    van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W; Mattson, Mark P

    2014-11-12

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect brain health. By enhancing neurogenesis, synaptic plasticity and neuronal stress robustness, exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems that mediate peripheral health benefits of intermittent energetic challenges have recently been described. A better understanding of adaptive neural response pathways activated by energetic challenges will enable the development and optimization of interventions to reduce the burden of disease in our communities. Copyright © 2014 the authors 0270-6474/14/3415139-11$15.00/0.

  19. Effects of intravenous glucose on Dopaminergic function in the human brain in vivo

    NARCIS (Netherlands)

    Haltia, Lauri T.; Rinne, Juha O.; Merisaari, Harri; Maguire, Ralph P.; Savontaus, Eriika; Helin, Semi; Nagren, Kjell; Kaasinen, Valtteri

    Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that

  20. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...... as an internal standard in stroke patients....

  1. Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

    Science.gov (United States)

    Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

    2013-12-01

    Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

  2. Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

    DEFF Research Database (Denmark)

    Madsen, P L; Hasselbalch, S G; Hagemann, L P

    1995-01-01

    fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic......Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety......-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation...

  3. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  4. Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Radka Gromnicova

    Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

  5. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    DEFF Research Database (Denmark)

    Stender, Johan; Kupers, Ron; Rodell, Anders

    2015-01-01

    of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global......The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function...... these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 October 2014; doi:10...

  6. Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2008-04-01

    Full Text Available The use of stimulants (methylphenidate and amphetamine as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations given with and without methylphenidate (20 mg, oral. Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less. This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering or impaired (i.e., attention deficit hyperactivity disorder, but it could be detrimental when

  7. Localization and mobility of glucose-coated gold nanoparticles within the brain.

    Science.gov (United States)

    Gromnicova, Radka; Yilmaz, Canan Ugur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather; Williams, Phil; Romero, Ignacio A; Sharrack, Basil; Male, David

    2016-03-01

    To identify the localization of glucose-coated gold nanoparticles within cells of the brain after intravascular infusion which may point to the mechanism by which they cross the blood-brain barrier. Tissue distribution of the nanoparticles was measured by inductively-coupled-mass spectrometry and localization within the brain by histochemistry and electron microscopy. Nanoparticles were identified within neurons and glial cells more than 10 μm from the nearest microvessel within 10 min of intracarotid infusion. Their distribution indicated movement across the endothelial cytosol, and direct transfer between cells of the brain. The rapid movement of this class of nanoparticle (brain demonstrates their potential to carry therapeutic biomolecules or imaging reagents.

  8. Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

    Science.gov (United States)

    Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

    2012-01-01

    Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

  9. Detection of glucose in the human brain with 1 H MRS at 7 Tesla.

    Science.gov (United States)

    Kaiser, Lana G; Hirokazu, Kawaguchi; Fukunaga, Masaki; B Matson, Gerald

    2016-12-01

    A new method is proposed for noninvasive detection of glucose in vivo using proton MR spectroscopy at 7 Tesla. The proposed method utilizes J-difference editing to uncover the resonance of beta-glucose (β-glc) at 3.23 ppm, which is strongly overlapped with choline. Calculations using the density matrix formalism are used to maximize the signal-to-noise ratio of the β-glc resonance at 3.23 ppm. The calculations are verified using phantom and in vivo data collected at 7 Tesla. The proposed method allows observation of the glucose signal at 3.23 ppm in the human brain spectrum. Additional co-edited resonances of N-acetylaspartylglutamatate and glutathione are also detected in the same experiment. The proposed method does not require carbon ( 13 C)- labeled glucose injections and 13 C hardware; as such, it has a potential to provide valuable information on intrinsic glucose concentration in the human brain in vivo. Magn Reson Med 76:1653-1660, 2016. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  10. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    Energy Technology Data Exchange (ETDEWEB)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

    2014-04-15

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  11. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    International Nuclear Information System (INIS)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Polidori, M.C.; Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia; Morbelli, Silvia; Bossert, Irene; Fiorucci, Giuliana; Dottorini, Massimo Eugenio

    2014-01-01

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain 18 F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  12. Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

    Science.gov (United States)

    Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

    2012-01-01

    Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

  13. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Low doses of alcohol substantially decrease glucose metabolism in the human brain.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

    2006-01-01

    Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

  15. Quantitative autoradiography of 14C-D-glucose metabolism of normal and traumatized rat brain using micro-absorption photometry

    International Nuclear Information System (INIS)

    Bonorden, S.

    1980-01-01

    It could be shown using 14 C-glucose as energy-providing substrate for brain tissue metabolism that for bolus type application a retarded and even channelling of the substrate into the metabolic process takes place. The presence of tracer in the tissue was established using autoradiography. A linear correlation between the amount of tissue-incorporated 14 C section thickness and exposure time could be established by means of densitometric measurement of brain sections of various thicknesses, by applying various 14 C-activities and by different exposure times. From these correlations direct conclusions may be made regarding the specific activity of the tissue provided that exposure time and section thickness of the sample are known. Comparative studies between cortex and narrow and between traumatized and non-traumatized brain tissue show that the rate of metabolism in brain cortex is markedly higher than in the marrow and that 14 C-incorporation is higher in traumatized tissue than in non-traumatized tissue. Whilst the difference in rate of metabolism between brain cortex and marrow can be clearly related to the differing cell count/unit surface area for cortex and marrow, the different energy conversion rates for functionally damaged and normal brain tissue is a specific characteristic of injury. Apart from the fact that an increased 14 C-deposition is in no way indicative of an increased metabolic activity, the possibility of quantifying 14 C-tissue content provides a basis for estimating therapeutic effects e.g. in the treatment of trauma-caused brain edema. (orig.) [de

  16. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  17. Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

    Science.gov (United States)

    Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

    2015-02-05

    Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  18. Ethylene glycol ethers induce apoptosis and disturb glucose metabolism in the rat brain.

    Science.gov (United States)

    Pomierny, Bartosz; Krzyżanowska, Weronika; Niedzielska, Ewa; Broniowska, Żaneta; Budziszewska, Bogusława

    2016-02-01

    Ethylene glycol ethers (EGEs) are compounds widely used in industry and household products, but their potential, adverse effect on brain is poorly understood, so far. The aim of the present study was to determine whether 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE), and 2-ethoxyethanol (EE) induces apoptotic process in the rat hippocampus and frontal cortex, and whether their adverse effect on the brain cells can result from disturbances in the glucose metabolism. Experiments were conducted on 40 rats, exposed to BE, PHE, EE, saline or sunflower oil for 4 weeks. Markers of apoptosis and glucose metabolism were determined in frontal cortex and hippocampus by western blot, ELISA, and fluorescent-based assays. BE and PHE, but not EE, increased expression of the active form of caspase-3 in the examined brain regions. BE and PHE increased caspase-9 level in the cortex and PHE also in the hippocampus. BE and PHE increased the level of pro-apoptotic proteins (Bax, Bak) and/or reduced the concentration of anti-apoptotic proteins (Bcl-2, Bcl-xL); whereas, the effect of BE was observed mainly in the cortex and that of PHE in the hippocampus. It has also been found that PHE increased brain glucose level, and both BE and PHE elevated pyruvate and lactate concentration. It can be concluded that chronic treatment with BE and PHE induced mitochondrial pathway of apoptosis, and disturbed glucose metabolism in the rat brain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Directory of Open Access Journals (Sweden)

    Wei-Ling Li

    2015-01-01

    Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  20. Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

    Science.gov (United States)

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S.; Telang, Frank; Alexoff, Dave; Logan, Jean; Wong, Christopher

    2011-01-01

    Context The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Design, Setting, and Participants Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with (18F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes (“on” condition) and once with both cell phones deactivated (“off” condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm3) and P < .05 (corrected for multiple comparisons) were considered significant. Main Outcome Measure Brain glucose metabolism computed as absolute metabolism (µmol/100 g per minute) and as normalized metabolism (region/whole brain). Results Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 µmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67–4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001

  1. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    International Nuclear Information System (INIS)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  2. Effects of intravenous glucose on dopaminergic function in the human brain in vivo.

    Science.gov (United States)

    Haltia, Lauri T; Rinne, Juha O; Merisaari, Harri; Maguire, Ralph P; Savontaus, Eriika; Helin, Semi; Någren, Kjell; Kaasinen, Valtteri

    2007-09-01

    Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

  3. Rapid discrimination of visual scene content in the human brain

    Science.gov (United States)

    Anokhin, Andrey P.; Golosheykin, Simon; Sirevaag, Erik; Kristjansson, Sean; Rohrbaugh, John W.; Heath, Andrew C.

    2007-01-01

    The rapid evaluation of complex visual environments is critical for an organism's adaptation and survival. Previous studies have shown that emotionally significant visual scenes, both pleasant and unpleasant, elicit a larger late positive wave in the event-related brain potential (ERP) than emotionally neutral pictures. The purpose of the present study was to examine whether neuroelectric responses elicited by complex pictures discriminate between specific, biologically relevant contents of the visual scene and to determine how early in the picture processing this discrimination occurs. Subjects (n=264) viewed 55 color slides differing in both scene content and emotional significance. No categorical judgments or responses were required. Consistent with previous studies, we found that emotionally arousing pictures, regardless of their content, produce a larger late positive wave than neutral pictures. However, when pictures were further categorized by content, anterior ERP components in a time window between 200−600 ms following stimulus onset showed a high selectivity for pictures with erotic content compared to other pictures regardless of their emotional valence (pleasant, neutral, and unpleasant) or emotional arousal. The divergence of ERPs elicited by erotic and non-erotic contents started at 185 ms post-stimulus in the fronto-central midline regions, with a later onset in parietal regions. This rapid, selective, and content-specific processing of erotic materials and its dissociation from other pictures (including emotionally positive pictures) suggests the existence of a specialized neural network for prioritized processing of a distinct category of biologically relevant stimuli with high adaptive and evolutionary significance. PMID:16712815

  4. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Dyve, S [Department of General Physiology and Biophysics, Panum Institute, Copenhagen (Denmark); Gjedde, A [Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal, Quebec (Canada)

    1991-01-01

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +- 2 {mu}mol hg{sup -1} min{sup -1}. (author).

  5. Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

    Science.gov (United States)

    Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

    2017-04-01

    The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

  6. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  7. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Science.gov (United States)

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  8. Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest.

    Science.gov (United States)

    Tomasi, Dardo G; Shokri-Kojori, Ehsan; Wiers, Corinde E; Kim, Sunny W; Demiral, Şukru B; Cabrera, Elizabeth A; Lindgren, Elsa; Miller, Gregg; Wang, Gene-Jack; Volkow, Nora D

    2017-12-01

    It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

  9. Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

    Science.gov (United States)

    Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

    2011-01-01

    Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

  10. Brain glucose overexposure and lack of acute metabolic flexibility in obesity and type 2 diabetes: a PET-[18F]FDG study in Zucker and ZDF rats

    OpenAIRE

    Liistro, Tiziana; Guiducci, Letizia; Burchielli, Silvia; Panetta, Daniele; Belcari, Nicola; Pardini, Silvia; Guerra, Alberto Del; Salvadori, Piero A; Iozzo, Patricia

    2010-01-01

    Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and ...

  11. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

  12. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  13. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  14. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Science.gov (United States)

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  15. Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

    Science.gov (United States)

    Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

    2016-10-01

    This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. It is determined whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was examined in a group of 72 subjects, ages 22 to 82 years, with 36 regions of interest chosen from both hemispheres of the cortex, midbrain and cerebellum. To determine metabolic rates the in-vivo technique of positron emission tomography (PET) was employed. Three age groups were chosen to compare hemispherical differences. In both young and intermediate age groups the left hemisphere had higher rCMRGlu values than those of the right for the majority of regions with, although less pronounced in the intermediate group. Importantly, the older age group displayed little difference between hemispheres. (author)

  17. Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

    Science.gov (United States)

    Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

    2016-08-01

    The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

    Science.gov (United States)

    Butterfield, D Allan; Lange, Miranda L Bader

    2009-11-01

    Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

  19. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

  20. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  1. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

    Science.gov (United States)

    Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

    2012-07-01

    Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

    Science.gov (United States)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

    2015-08-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.

  3. Maternal high-fat feeding leads to alterations of brain glucose metabolism in the offspring: positron emission tomography study in a porcine model.

    Science.gov (United States)

    Sanguinetti, Elena; Liistro, Tiziana; Mainardi, Marco; Pardini, Silvia; Salvadori, Piero A; Vannucci, Alessandro; Burchielli, Silvia; Iozzo, Patricia

    2016-04-01

    Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.

  4. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  5. Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice.

    Science.gov (United States)

    Wang, Pengwen; Su, Caixin; Feng, Huili; Chen, Xiaopei; Dong, Yunfang; Rao, Yingxue; Ren, Ying; Yang, Jinduo; Shi, Jing; Tian, Jinzhou; Jiang, Shucui

    2017-03-01

    Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aβ40, Aβ42 and Aβ-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling. We hypothesised that curcumin might target both the glucose metabolism and insulin signalling pathways. In this study, we monitored brain glucose metabolism in living APPswe/PS1dE9 double transgenic mice using a micro-positron emission tomography (PET) technique. The study showed an improvement in cerebral glucose uptake in AD mice. For a more in-depth study, we used immunohistochemical (IHC) staining and western blot techniques to examine key factors in both glucose metabolism and brain insulin signalling pathways. The results showed that curcumin ameliorated the defective insulin signalling pathway by upregulating insulin-like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression while downregulating IR and IRS-1. Our study found that curcumin improved spatial learning and memory, at least in part, by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain.

  6. Effects of glucose, insulin, and supernatant from pancreatic beta-cells on brain-pancreas relative protein in rat hippocampus

    NARCIS (Netherlands)

    Lin, Yan-Hua; Westenbroek, Christel; Tie, Lu; Liu, Ai-Hua; Yu, He-Ming; Ter Horst, Gert J.; Li, Xue-Jun

    2006-01-01

    Brain-pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied by changes in insulin and glucose levels, and that expression

  7. Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.

    Science.gov (United States)

    Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

  8. Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

    Science.gov (United States)

    Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

    2015-12-01

    Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

  9. Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

    Science.gov (United States)

    Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

    2015-01-01

    Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (pblood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

  10. Does sugar content matter? Blood plasma glucose levels in an occasional and a specialist avian nectarivore.

    Science.gov (United States)

    Witteveen, Minke; Brown, Mark; Downs, Colleen T

    2014-01-01

    Nectar composition within a plant pollinator group can be variable, and bird pollinated plants can be segregated into two groups based on their adaptations to either a specialist or an occasional bird pollination system. Specialist nectarivores rely primarily on nectar for their energy requirements, while occasional nectarivores meet their energy requirements from nectar as well as from seeds, fruit and insects. Avian blood plasma glucose concentration (PGlu) is generally high compared with mammals. It is also affected by a range of factors including species, gender, age, ambient temperature, feeding pattern, reproductive status, circadian rhythm and moult status, among others. We examined whether sugar content affected PGlu of two avian nectarivores, a specialist nectarivore the Amethyst Sunbird Chalcomitra amethystina, and an occasional nectarivore the Cape White-eye Zosterops virens, when fed sucrose-hexose sugar solution diets of varying concentrations (5%-35%). Both species regulated PGlu within a range which was affected by sampling time (fed or fasted) and not dietary sugar concentration. The range in mean PGlu was broader in Amethyst Sunbirds (11.52-16.51mmol/L) compared with Cape White-eyes (14.33-15.85mmol/L). This suggests that these birds are not constrained by dietary sugar concentration with regard to PGlu regulation, and consequently selective pressure on plants for their nectar characteristics is due to reasons other than glucose regulation. © 2013.

  11. Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

    Science.gov (United States)

    Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

    2011-04-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Alf, Malte F; Duarte, João M N; Schibli, Roger; Gruetter, Rolf; Krämer, Stefanie D

    2013-12-01

    We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. 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-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics. Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

  13. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism......, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (Psuicide attempts (P=.021). IGM moderated...... the association between BDNF and the number of previous mood episodes (P

  14. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients...... with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...

  15. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P cerebral cortex as a whole compared...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

  16. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

    Science.gov (United States)

    Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2014-04-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are

  17. D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    International Nuclear Information System (INIS)

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V.

    1990-01-01

    We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects

  18. Glucose and oxygen metabolism after penetrating ballistic-like brain injury

    Science.gov (United States)

    Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

  19. Brain serotonin content - Increase following ingestion of carbohydrate diet.

    Science.gov (United States)

    Fernstrom, J. D.; Wurtman, R. J.

    1971-01-01

    In the rat, the injection of insulin or the consumption of carbohydrate causes sequential increases in the concentrations of tryptophan in the plasma and the brain and of serotonin in the brain. Serotonin-containing neurons may thus participate in systems whereby the rat brain integrates information about the metabolic state in its relation to control of homeostasis and behavior.

  20. Novel MRI methodology to detect human whole-brain connectivity changes after ingestion of fructose or glucose

    Science.gov (United States)

    Tsao, Sinchai; Wilkins, Bryce; Page, Kathleen A.; Singh, Manbir

    2012-03-01

    A novel MRI protocol has been developed to investigate the differential effects of glucose or fructose consumption on whole-brain functional brain connectivity. A previous study has reported a decrease in the fMRI blood oxygen level dependent (BOLD) signal of the hypothalamus following glucose ingestion, but due to technical limitations, was restricted to a single slice covering the hypothalamus, and thus unable to detect whole-brain connectivity. In another previous study, a protocol was devised to acquire whole-brain fMRI data following food intake, but only after restricting image acquisition to an MR sampling or repetition time (TR) of 20s, making the protocol unsuitable to detect functional connectivity above 0.025Hz. We have successfully implemented a continuous 36-min, 40 contiguous slices, whole-brain BOLD acquisition protocol on a 3T scanner with TR=4.5s to ensure detection of up to 0.1Hz frequencies for whole-brain functional connectivity analysis. Human data were acquired first with ingestion of water only, followed by a glucose or fructose drink within the scanner, without interrupting the scanning. Whole-brain connectivity was analyzed using standard correlation methodology in the 0.01-0.1 Hz range. The correlation coefficient differences between fructose and glucose ingestion among targeted regions were converted to t-scores using the water-only correlation coefficients as a null condition. Results show a dramatic increase in the hypothalamic connectivity to the hippocampus, amygdala, insula, caudate and the nucleus accumben for fructose over glucose. As these regions are known to be key components of the feeding and reward brain circuits, these results suggest a preference for fructose ingestion.

  1. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

  2. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

    Science.gov (United States)

    Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

    2003-04-15

    Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

  3. Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Borra, Ronald; Lautamaki, Riikka; Parkkola, Riitta; Komu, Markku; Sijens, Paul E.; Hallsten, Kirstl; Bergman, Jorgen; Iozzo, Patricia; Nuutila, Pirjo

    2008-01-01

    The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was

  4. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    Science.gov (United States)

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

  5. Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

    Science.gov (United States)

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2015-12-01

    There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

  6. Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, A.; Sako, K.; Diksic, M.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using YF-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of YF. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

  7. Electrochemical Glucose Oxidation Using Glassy Carbon Electrodes Modified with Au-Ag Nanoparticles: Influence of Ag Content

    Directory of Open Access Journals (Sweden)

    Nancy Gabriela García-Morales

    2015-01-01

    Full Text Available This paper describes the application of glassy carbon modified electrodes bearing Aux-Agy nanoparticles to catalyze the electrochemical oxidation of glucose. In particular, the paper shows the influence of the Ag content on this oxidation process. A simple method was applied to prepare the nanoparticles, which were characterized by transmission electron microscopy, Ultraviolet-Visible spectroscopy, X-ray diffraction spectroscopy, and cyclic voltammetry. These nanoparticles were used to modify glassy carbon electrodes. The effectiveness of these electrodes for electrochemical glucose oxidation was evaluated. The modified glassy carbon electrodes are highly sensitive to glucose oxidation in alkaline media, which could be attributed to the presence of Aux-Agy nanoparticles on the electrode surface. The voltammetric results suggest that the glucose oxidation speed is controlled by the glucose diffusion to the electrode surface. These results also show that the catalytic activity of the electrodes depends on the Ag content of the nanoparticles. Best results were obtained for the Au80-Ag20 nanoparticles modified electrode. This electrode could be used for Gluconic acid (GA production.

  8. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

    Science.gov (United States)

    Luo, Shan; Monterosso, John R; Sarpelleh, Kayan; Page, Kathleen A

    2015-05-19

    Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

  9. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  10. Electro-physiological changes in the brain induced by caffeine or glucose nasal spray.

    Science.gov (United States)

    De Pauw, K; Roelands, B; Van Cutsem, J; Marusic, U; Torbeyns, T; Meeusen, R

    2017-01-01

    A direct link between the mouth cavity and the brain for glucose (GLUC) and caffeine (CAF) has been established. The aim of this study is to determine whether a direct link for both substrates also exist between the nasal cavity and the brain. Ten healthy male subjects (age 22 ± 1 years) performed three experimental trials, separated by at least 2 days. Each trial included a 20-s nasal spray (NAS) period in which solutions placebo (PLAC), GLUC, or CAF were provided in a double-blind, randomized order. During each trial, four cognitive Stroop tasks were performed: two familiarization trials and one pre- and one post-NAS trial. Reaction times and accuracy for different stimuli (neutral, NEUTR; congruent, CON; incongruent INCON) were determined. Electroencephalography was continuously measured throughout the trials. During the Stroop tasks pre- and post-NAS, the P300 was assessed and during NAS, source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA). NAS activated the anterior cingulate cortex (ACC). CAF-NAS also increased θ and β activity in frontal cortices. Furthermore, GLUC-NAS increased the β activity within the insula. GLUC-NAS also increased the P300 amplitude with INCON (P = 0.046) and reduced P300 amplitude at F3-F4 and P300 latency at CP1-CP2-Cz with NEUTR (P = 0.001 and P = 0.016, respectively). The existence of nasal bitter and sweet taste receptors possibly induce these brain responses. Greater cognitive efficiency was observed with GLUC-NAS. CAF-NAS activated cingulate, insular, and sensorymotor cortices, whereas GLUC-NAS activated sensory, cingulate, and insular cortices. However, no effect on the Stroop task was found.

  11. Monitoring arterio-venous differences of glucose and lactate in the anesthetized rat with or without brain damage with ultrafiltration and biosensor technology

    NARCIS (Netherlands)

    Leegsma-Vogt, G; Venema, K; Postema, F; Korf, J

    2001-01-01

    Continuous monitoring of arterio-venous glucose and lactate differences may serve as a diagnostic tool to assess normal brain function and brain pathology. We describe a method and some results obtained with arterio-venous measurements of glucose and lactate in the blood of the

  12. Cellular localization of 2-[3H]deoxy-D-glucose from paraffin-embedded brains

    International Nuclear Information System (INIS)

    Durham, D.; Woolsey, T.A.; Kruger, L.

    1981-01-01

    Results of experiments in which regional neuronal activity is revealed by a 2-[ 3 H]deoxy-D-glucose ( 3 H-2-DG)-paraffin section-emulsion autoradiography method are described. The trigeminal pathway of freely behaving mice was activated differentially by selective patterns of whisker removal. One hour after injection of concentrated 3 H-2-DG, the animals were perfused systemically with a periodate/lysine/paraformaldehyde mixture the brains were embedded in paraffin, and serial sections were taken and coated with emulsion for autoradiography. Diffusion of the isotope out of the tissue was assessed visually and by liquid scintillation counting. While substantial loss of 3 H isotope into the embedding fluids (about 95%) was found, the scintillation counts and the autoradiograms showed good fixation of the isotope in situ, no evidence of isotope movement into the emulsion, and no gradients of diffusion in the sectioned material. Patterns of regional labeling were similar to those reported from brains prepared by conventional 2-[ 14 C]deoxy-D-glucose ( 14 C-2-DG) autoradiography; Trigeminal structures associated with the intact (stimulated) whiskers were labeled relatively heavily, indicating that label uptake is specific with respect to neuronal activity. In the cortex, the patterns of label corresponded directly and precisely to those barrels known to receive inputs from the intact whiskers. Distribution of silver grains in the cortex and in the brainstem was correlated directly with neuronal profiles. Clearly, this approach offers considerable technical advantages, in particular, the ease with which the histological material is prepared. The resolution of the autoradiograms and the quality of the histology are excellent

  13. Brain Transport Profiles of Ginsenoside Rb1 by Glucose Transporter 1: In Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Yu-Zhu Wang

    2018-04-01

    Full Text Available Ginsenoside Rb1 (Rb1 has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood–brain barrier (BBB using primary cultured rat brain microvascular endothelial cells (rBMEC, an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb1 into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v. to normal rats for consecutive 1 week before Rb1 (10 mg/kg, i.v. at 0.5, 2, and 6 h did not alter Rb1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively. The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb1 at the BBB is at least partly mediated by GLUT1 transporter.

  14. Brain size and white matter content of cerebrospinal tracts determine the upper cervical cord area: evidence from structural brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Engl, Christina; Arsic, Milan; Boucard, Christine C.; Biberacher, Viola; Nunnemann, Sabine; Muehlau, Mark [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Technische Universitaet Muenchen, TUM-Neuroimaging Center, Klinikum rechts der Isar, Munich (Germany); Schmidt, Paul [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Ludwig-Maximilians-University Muenchen, Department of Statistics, Munich (Germany); Roettinger, Michael [Technische Universitaet Muenchen, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Muenchner Institut fuer Neuroradiologie, Munich (Germany); Etgen, Thorleif [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Klinikum Traunstein, Department of Neurology, Traunstein (Germany); Koutsouleris, Nikolaos; Meisenzahl, Eva M. [Ludwig-Maximilians-Universitaet Muenchen, Department of Psychiatry and Psychotherapy, Munich (Germany); Reiser, Maximilian [Ludwig-Maximilians-Universitaet, Department of Radiology, Munich (Germany)

    2013-08-15

    Measurement of the upper cervical cord area (UCCA) from brain MRI may be an effective way to quantify spinal cord involvement in neurological disorders such as multiple sclerosis. However, knowledge on the determinants of UCCA in healthy controls (HCs) is limited. In two cohorts of 133 and 285 HCs, we studied the influence of different demographic, body-related, and brain-related parameters on UCCA by simple and partial correlation analyses as well as by voxel-based morphometry (VBM) across both cerebral gray matter (GM) and white matter (WM). First, we confirmed the known but moderate effect of age on UCCA in the older cohort. Second, we studied the correlation of UCCA with sex, body height, and total intracranial volume (TIV). TIV was the only variable that correlated significantly with UCCA after correction for the other variables. Third, we studied the correlation of UCCA with brain-related parameters. Brain volume correlated stronger with UCCA than TIV. Both volumes of the brain tissue compartments GM and WM correlated with UCCA significantly. WM volume explained variance of UCCA after correction for GM volume, whilst the opposite was not observed. Correspondingly, VBM did not yield any brain region, whose GM content correlated significantly with UCCA, whilst cerebral WM content of cerebrospinal tracts strongly correlated with UCCA. This latter effect increased along a craniocaudal gradient. UCCA is mainly determined by brain volume as well as by WM content of cerebrospinal tracts. (orig.)

  15. Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment.

    Science.gov (United States)

    Porto, Fábio Henrique de Gobbi; Coutinho, Artur Martins Novaes; Pinto, Ana Lucia de Sá; Gualano, Bruno; Duran, Fabio Luís de Souza; Prando, Silvana; Ono, Carla Rachel; Spíndola, Lívia; de Oliveira, Maira Okada; do Vale, Patrícia Helena Figuerêdo; Nitrini, Ricardo; Buchpiguel, Carlos Alberto; Brucki, Sonia Maria Dozzi

    2015-01-01

    Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

  16. Study of the brain glucose metabolism in different stage of mixed-type multiple system atrophy

    International Nuclear Information System (INIS)

    Wang Ying; Zhang Benshu; Cai Li; Zhang Meiyun; Gao Shuo

    2014-01-01

    Objective: To investigate the brain glucose metabolism in different stage of mixed-type multiple system atrophy (MSA). Methods: Forty-six MSA patients with cerebellar or Parkinsonian symptoms and 18 healthy controls with similar age as patients were included. According to the disease duration,the patients were divided into three groups: group 1 (≤ 12 months, n=14), group 2 (13-24 months, n=13), group 3 (≥ 25 months, n=19). All patients and controls underwent 18 F-FDG PET/CT brain imaging. To compare metabolic distributions between different groups, SPM 8 software and two-sample t test were used for image data analysis. When P<0.005, the result was considered statistically significant. Results: At the level of P<0.005, the hypometabolism in group 1 (all t>3.49) was identified in the frontal lobe, lateral temporal lobe, insula lobe, anterior cingulate cortex, caudate nucleus and anterior cerebellar hemisphere. The regions of hypometabolism extended to posterolateral putamen and part of posterior cerebellar hemisphere in group 2 (all t>3.21). In group 3, the whole parts of putamen and cerebellar hemisphere were involved as hypometabolism (all t>4.08). In addition to the hypometabolism regions, there were also stabled hypermetabolism regions mainly in the parietal lobe, medial temporal lobe and the thalamus in all patient groups (all t>3.27 in group 1, all t>3.02 in group 2,all t>3.30 in group 3). Conclusions: Disease duration is closely related to the FDG metabolism in the MSA patients. Frontal lobe, lateral temporal lobe, anterior cingulate cortex and caudate nucleus can be involved at early stage of the disease. Putaminal hypometabolism begins in its posterolateral part. Cerebellar hypometabolism occurs early at its anterior part. Besides, thalamus shows hypermetabolism in the whole duration. 18 F-FDG metabolic changes of brain can reflect the development of mixed-type MSA. (authors)

  17. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  18. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

    Science.gov (United States)

    Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

    2002-03-01

    Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

  19. Twitter and traumatic brain injury: A content and sentiment analysis of tweets pertaining to sport-related brain injury.

    Science.gov (United States)

    Workewych, Adriana M; Ciuffetelli Muzzi, Madeline; Jing, Rowan; Zhang, Stanley; Topolovec-Vranic, Jane; Cusimano, Michael D

    2017-01-01

    Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player's life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users' messages often reflects the prevailing culture related to a particular event or health issue. We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter ® tweets related to traumatic brain injuries in sports collected during June and July 2013. We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies.

  20. Brain Based Learning in Science Education in Turkey: Descriptive Content and Meta Analysis of Dissertations

    Science.gov (United States)

    Yasar, M. Diyaddin

    2017-01-01

    This study aimed at performing content analysis and meta-analysis on dissertations related to brain-based learning in science education to find out the general trend and tendency of brain-based learning in science education and find out the effect of such studies on achievement and attitude of learners with the ultimate aim of raising awareness…

  1. Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

    Science.gov (United States)

    Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

    2017-08-01

    Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

  2. Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients.

    Science.gov (United States)

    Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L

    2014-04-16

    We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

    Science.gov (United States)

    Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

    2016-11-01

    Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

    2015-01-01

    To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  5. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Christian-Alexandre Castellano

    Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  6. Evaluation of glucose and insulin response to haylage diets with different content of nonstructural carbohydrates in 2 breeds of horses.

    Science.gov (United States)

    Lindåse, S; Müller, C; Nostell, K; Bröjer, J

    2018-04-09

    Information about the effect of nonstructural carbohydrates (NSCs) in forage on the postprandial glucose and insulin response in horses is scarce. This is of interest as postprandial hyperinsulinemia in horses is a risk factor for laminitis. In addition, insulin sensitivity (IS) differs between breeds. The aim was to evaluate the postprandial glucose and insulin response to haylage diets with different NSC content in horses of 2 different breeds and to evaluate the relationship between the postprandial insulin response and measures of IS derived from a frequently sampled intravenous glucose tolerance test (FSIGTT). Standardbreds (n = 9) and Icelandic horses (n = 9) with a mean body condition score of 5.5 ± 0.6 (scale 1-9) were studied. Horses were clinically healthy at the start of the study and had no history of endocrinopathic laminitis. The experiment was conducted as a replicate 3 × 3 Latin square, in which horses were fed haylage diets with low (4.2%), medium (13.6%), and high (18.2%) NSC content of dry matter. Blood sampling was performed before feeding and every 30 min until 300 min after feeding. An FSIGTT was also performed in all horses. The early (first 60 min) and the total (300 min) postprandial glucose and insulin response (area under the curve [AUC]) was higher after a meal of both medium and high NSC haylage in comparison with low NSC haylage when both breeds were combined (P ≤ 0.02). There was a main effect of breed for the early (P ≤ 0.004) but not for the total (P > 0.12) postprandial glucose and insulin response. The IS index was comparable between breeds (P = 0.75). The natural logarithm of the peak concentration, the AUC for the first 60 min and the total AUC for insulin, after a meal of medium and high NSC haylage, were moderately negatively correlated (P haylage with low NSC content (P > 0.054). This study demonstrates that the postprandial insulin response is affected by both the NSC content of haylage and the horse's IS. However

  7. Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

    Science.gov (United States)

    Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Fernández, Cecilia; Rubio, Juan J; Mucientes, Jorge; Rodriguez, Begoña; Blanco, Edelio; Donis, Luis

    2017-01-01

    Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  8. The role of glycogen, glucose and lactate in neuronal activity during hypoxia in the hooded seal (Cystophora cristata) brain.

    Science.gov (United States)

    Czech-Damal, N U; Geiseler, S J; Hoff, M L M; Schliep, R; Ramirez, J-M; Folkow, L P; Burmester, T

    2014-09-05

    The brains of diving mammals are repeatedly exposed to hypoxic conditions during diving. Brain neurons of the hooded seal (Cystophora cristata) have been shown to be more hypoxia tolerant than those of mice, but the underlying mechanisms are not clear. Here we investigated the roles of different metabolic substrates for maintenance of neuronal activity and integrity, by comparing the in vitro spontaneous neuronal activity of brain slices from layer V of the visual cortex of hooded seals with those in mice (Mus musculus). Studies were conducted by manipulating the composition of the artificial cerebrospinal fluid (aCSF), containing either 10 mM glucose, or 20 mM lactate, or no external carbohydrate supply (aglycemia). Normoxic, hypoxic and ischemic conditions were applied. The lack of glucose or the application of lactate in the aCSF containing no glucose had little effect on the neuronal activity of seal neurons in either normoxia or hypoxia, while neurons from mice survived in hypoxia only few minutes regardless of the composition of the aCSF. We propose that seal neurons have higher intrinsic energy stores. Indeed, we found about three times higher glycogen stores in the seal brain (∼4.1 ng per μg total protein in the seal cerebrum) than in the mouse brain. Notably, in aCSF containing no glucose, seal neurons can tolerate 20 mM lactate while in mouse neuronal activity vanished after few minutes even in normoxia. This can be considered as an adaptation to long dives, during which lactate accumulates in the blood. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Otte, A. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland)]|[Department of Nuclear Medicine, University Hospital Freiburg (Germany); Weiner, S.M. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Peter, H.H. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Mueller-Brand, J. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Goetze, M. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Moser, E. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Gutfleisch, J. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Hoegerle, S. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Juengling, F.D. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Nitzsche, E.U. [Department of Nuclear Medicine, University Hospital Freiburg (Germany)

    1997-07-01

    In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40{+-}14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40{+-}12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922{+-}0.045 in patients and 1.066{+-}0.081 in controls (P<0.0001, Mann Whitney U test), while on the left side it was 0.892{+-}0.060 in patients and 1.034{+-}0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease. (orig.). With 1 fig., 1 tab.

  10. Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study

    International Nuclear Information System (INIS)

    Otte, A.; Weiner, S.M.; Peter, H.H.; Mueller-Brand, J.; Goetze, M.; Moser, E.; Gutfleisch, J.; Hoegerle, S.; Juengling, F.D.; Nitzsche, E.U.

    1997-01-01

    In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40±14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40±12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922±0.045 in patients and 1.066±0.081 in controls (P<0.0001, Mann Whitney U test), while on the left side it was 0.892±0.060 in patients and 1.034±0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease. (orig.). With 1 fig., 1 tab

  11. The effect of glucose stimulation on 45calcium uptake of rat pancreatic islets and their total calcium content as measured by a fluorometric micro-method

    International Nuclear Information System (INIS)

    Wolters, G.H.J.; Wiegman, J.B.; Konijnendijk, W.

    1982-01-01

    Glucose-stimulated 45 calcium uptake and total calcium content of rat pancreatic islets has been studied, using a new fluorometric micro-method to estimate total calcium. Extracellular calcium was separated from incubated tissue by a rapid micro-filtration procedure. Islets incubated up to 60 min with calcium chloride 2.5 mmol/l and glucose 2.5 mmol/l maintained the same calcium content (670 +- 7.5 pmol/μg DNA). When the glucose concentration was raised to 15 mmol/l no change in the total calcium content could be detected. On incubation with glucose 2.5 mmol/l in the absence of calcium, the calcium content decreased to 488 +- 27 pmol/μg DNA. On incubation with 45 calcium chloride 2.5 mmol/l for 5 or 30 min at 2.5 mmol/l glucose, islets exchanged 21 +- 2 and 28 +- 1% of their total calcium content and, at 15 mmol/l glucose, 30 +- 3 and 45 +- 2%, respectively. Thus, islet calcium has a high turn-over rate. Glucose stimulation results in an increase of the calcium uptake without enhancing the total calcium content and hence must increase the calcium-exchangeable pool. (orig.)

  12. Mitochondrial monoaminoxidase activity and serotonin content in rat brain after whole-body γ-irradiation

    International Nuclear Information System (INIS)

    Savitskij, I.V.; Tsybul'skij, V.V.; Grivtsev, B.A.

    1985-01-01

    It is shown that γ-irradiation of albino rats with a dose of 30 Gy leads to pronounced phase changes in monoaminoxidase activity and serotonin content in rat brain at early times after whole-body exposure. These is a similar direction of changes in the activity of the enzyme and in the content of the substrate adequate to the latter

  13. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

    OpenAIRE

    McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

    2015-01-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected ...

  14. Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation

    DEFF Research Database (Denmark)

    Steensberg, Adam; van Hall, Gerrit; Keller, Charlotte

    2002-01-01

    on two occasions: one after 60 min of two-legged cycling (16 h prior to the experimental trial) followed by a high carbohydrate diet (HCHO) and the other after the same exercise followed by a low carbohydrate diet (LCHO) (Series 2). Muscle glycogen was decreased by 40 % when comparing the pre-exercised......There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycogen concentration influences glucose uptake...... during exercise, 13 healthy men were studied during two series of experiments. Seven men completed 4 h of two-legged knee extensor exercise 16 h after reducing of muscle glycogen by completing 60 min of single-legged cycling (Series 1). A further six men completed 3 h of two-legged knee extensor exercise...

  15. Magnesium Affects Poly(3-hydroxybutyrate-co-4-hydroxybutyrate Content and Composition by Affecting Glucose Uptake in Delftia acidovorans

    Directory of Open Access Journals (Sweden)

    Lee, W. H.

    2007-01-01

    Full Text Available Precise control of polyhydroxyalkanoate (PHA composition is necessary in order to synthesize polymers with specific properties. Among the various types of PHA that have been identified, those that contain 4-hydroxybutyrate (4HB monomers are especially useful in the medical and pharmaceutical fields as absorbable biomaterial. In this study, we have investigated the effect of magnesium concentration on the biosynthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate [P(3HB-co-4HB] by Delftia acidovorans DS-17. Our results show that, magnesium affects the copolymer content and composition by affecting glucose uptake from the culture medium. Higher concentrations of magnesium resulted in lower molar fractions of 3HB in the copolymer and reduced uptake of glucose. The results show for the first time that magnesium may be used to achieve fine control of biologically synthesized PHA copolymer composition.

  16. Physiological Fluctuations in Brain Temperature as a Factor Affecting Electrochemical Evaluations of Extracellular Glutamate and Glucose in Behavioral Experiments

    Science.gov (United States)

    2013-01-01

    The rate of any chemical reaction or process occurring in the brain depends on temperature. While it is commonly believed that brain temperature is a stable, tightly regulated homeostatic parameter, it fluctuates within 1–4 °C following exposure to salient arousing stimuli and neuroactive drugs, and during different behaviors. These temperature fluctuations should affect neural activity and neural functions, but the extent of this influence on neurochemical measurements in brain tissue of freely moving animals remains unclear. In this Review, we present the results of amperometric evaluations of extracellular glutamate and glucose in awake, behaving rats and discuss how naturally occurring fluctuations in brain temperature affect these measurements. While this temperature contribution appears to be insignificant for glucose because its extracellular concentrations are large, it is a serious factor for electrochemical evaluations of glutamate, which is present in brain tissue at much lower levels, showing smaller phasic fluctuations. We further discuss experimental strategies for controlling the nonspecific chemical and physical contributions to electrochemical currents detected by enzyme-based biosensors to provide greater selectivity and reliability of neurochemical measurements in behaving animals. PMID:23448428

  17. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  18. Comparison of Trazodone, Diazepame and Dibenzepine Influences on Rat Brain Beta-Endorphins Content

    Directory of Open Access Journals (Sweden)

    Radivoj Jadrić

    2007-08-01

    Full Text Available The aim of our study was to establish the extent of influence of different psychotropic drugs to brain β-endorphins in experimental animals. The study was performed on albino Wistar rats (weight 250 g, treated with different psychoactive drugs. RIA technique was employed for quantification of brain β-endorphins. Brain β-endorphins were higher in experiment group treated with trazodone (929 pg/g ± 44,43; X±SD, and dibenzepine (906,63 pg/g ± 74,06, yet with lower brain content in rats treated with diazepame (841,55 pg/g ± 68,47, compared to brain β-endorphins content of control group treated with saline solution (0,95% NaCl (873,5 pg/g ± 44,89. Significant differences were obtained comparing brain β-endorphins of trazodone vs. diaze-pame treated animals, with diazepame group having lower values (p<0,02. This study showed differences in changes of rat brain β-endorphins contents when different psy-choactive drugs are used. Therefore, we consider that β-endorphins could be used for evaluation of effects of psychoactive drugs, as a useful parameter in therapy with these psycho pharmaceuticals.

  19. Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study.

    Science.gov (United States)

    Shijo, Katsunori; Sutton, Richard L; Ghavim, Sima S; Harris, Neil G; Bartnik-Olson, Brenda L

    2017-01-01

    Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13 C] glucose for 68 min 13 C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13 C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13 C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of

  20. Hierarchical clustering of Alzheimer and 'normal' brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2001-01-01

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element concentrations in the frontal lobe were determined for twenty six Alzheimer (15 male, 11 female) and twenty six 'normal' (8 male, 18 female) brain tissue samples. In the parietal lobe ten Alzheimer (2 male, 8 female) and ten 'normal' (8 male, 2 female) samples were taken along with ten Alzheimer (4 male, 6 female) and ten 'normal' (6 male, 4 female) from the occipital lobe. For the frontal lobe trace element concentrations were determined using proton induced X-ray emission (PIXE) analysis while in parietal and occipital regions instrumental neutron activation analysis (INAA) was used. Additionally eighteen Alzheimer (9 male, 9 female) and eighteen age matched 'normal' (8 male, 10 female) living subjects were examined using positron emission tomography (PET) in order to determine regional cerebral metabolic rates of glucose (rCMRGlu). The rCMRGlu of 36 regions of the brain was investigated including frontal, occipital and parietal lobes as in the trace element study. Hierarchical cluster analysis was applied to the trace element and glucose metabolism data to discover which variables in the resulting dendrograms displayed the most significant separation between Alzheimer and 'normal' subjects. (author)

  1. Is cerebral glucose metabolism related to blood–brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Francesco, Ursini; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Torniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

    2016-01-01

    Abstract The aim of this study was to investigate the relationships between blood–brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(18F) fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before 18F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and 18F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects. PMID:27631200

  2. Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

    Science.gov (United States)

    Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

    2016-01-01

    The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (Pbrain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

  3. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

    Science.gov (United States)

    Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

    2014-06-01

    Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

  5. Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

    Science.gov (United States)

    Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

    2015-07-01

    In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

  6. ONLINE MONITORING OF EXTRACELLULAR BRAIN GLUCOSE USING MICRODIALYSIS AND A NADPH-LINKED ENZYMATIC ASSAY

    NARCIS (Netherlands)

    VANDERKUIL, JHF; KORF, J

    A method to monitor extracellular glucose in freely moving rats, based on intracerebral microdialysis coupled to an enzyme reactor is described. The dialysate is continuously mixed with a solution containing the enzymes hexokinase and glucose-6-phosphate dehydrogenase, and the fluorescence of NADPH

  7. The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test.

    Science.gov (United States)

    Lee, I-Te; Chen, Chen-Huan; Wang, Jun-Sing; Fu, Chia-Po; Lee, Wen-Jane; Liang, Kae-Woei; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

    2018-01-01

    Arterial stiffening blunts postprandial vasodilatation. We hypothesized that brain-derived neurotrophic factor (BDNF) may modulate postprandial central pulse pressure, a surrogate marker for arterial stiffening. A total of 82 non-diabetic subjects received a 75-g oral glucose tolerance test (OGTT) after overnight fasting. Serum BDNF concentrations were determined at 0, 30, and 120min to calculate the area under the curve (AUC). Brachial and central blood pressures were measured using a noninvasive central blood pressure monitor before blood withdrawals at 0 and 120min. With the median AUC of BDNF of 45(ng/ml)∗h as the cutoff value, the central pulse pressure after glucose intake was significantly higher in the subjects with a low BDNF than in those with a high BDNF (63±16 vs. 53±11mmHg, P=0.003), while the brachial pulse pressure was not significantly different between the 2 groups (P=0.099). In a multivariate linear regression model, a lower AUC of BDNF was an independent predictor of a higher central pulse pressure after oral glucose intake (linear regression coefficient-0.202, 95% confidence interval-0.340 to -0.065, P=0.004). After oral glucose challenge, a lower serum BDNF response is significantly associated with a higher central pulse pressure. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

    Science.gov (United States)

    Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

    2015-08-01

    To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

  9. Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

    Science.gov (United States)

    Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

    2013-01-01

    Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

  10. Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

    2009-01-01

    This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

  11. The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

    Science.gov (United States)

    Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

    2017-07-03

    Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

  12. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    Directory of Open Access Journals (Sweden)

    Laurent Chazalviel

    2016-01-01

    Full Text Available Normobaric oxygen (NBO and hyperbaric oxygen (HBO are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO 2 = 1 atmospheres absolute (ATA = 0.1 MPa and HBO (pO 2 = 2.5 ATA = 0.25 MPa through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  13. Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Pizzolato, G; Soncrant, T T; Larson, D M; Rapoport, S I

    1987-08-01

    Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic (/sup 14/C)2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an atypical neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the typical neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.

  14. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    International Nuclear Information System (INIS)

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O'Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [ 14 C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor

  15. Brain regions involved in voluntary movements as revealed by radioisotopic mapping of CBF or CMR-glucose changes

    DEFF Research Database (Denmark)

    Lassen, N A; Ingvar, D H

    1990-01-01

    Mapping of cortical and subcortical grey matter active during voluntary movements by means of measurements of local increases of CBF or CMR-Glucose is reviewed. Most of the studies concern observations in man during hand movements using the intracarotid Xenon-133 injection technique, an approach...... that only allows to image the cortex of the hemisphere on one side (the injected side) of the brain. The results show that simple static or repetitive movements mainly activate the contralateral primary hand area (MI and SI); complex preprogrammed or spontaneous purposeful movements the supplementary motor...... area SMA on both sides increase in CBF/CMR-glucose and even internally ("mentally") going through the trained movements, causes such changes; complex purposeful movements also activate the premotor cortex, a response that is bilateral with greatest response contralaterally. Studies in patients...

  16. Glucose administration after traumatic brain injury exerts some benefits and no adverse effects on behavioral and histological outcomes

    Science.gov (United States)

    Shijo, Katsunori; Ghavim, Sima; Harris, Neil G.; Hovda, David A.; Sutton, Richard L.

    2015-01-01

    The impact of hyperglycemia after traumatic brain injury (TBI), and even the administration of glucose–containing solutions to head injured patients, remains controversial. In the current study adult male Sprague-Dawley rats were tested on behavioral tasks and then underwent surgery to induce sham injury or unilateral controlled cortical impact (CCI) injury followed by injections (i.p.) with either a 50% glucose solution (Glc; 2 g/kg) or an equivalent volume of either 0.9% or 8% saline (Sal) at 0, 1, 3 and 6 h post-injury. The type of saline treatment did not significantly affect any outcome measures, so these data were combined. Rats with CCI had significant deficits in beam-walking traversal time and rating scores (p’s glucose may improve some neurological outcomes and, importantly, the induction of hyperglycemia after isolated TBI did not adversely affect any sensorimotor, cognitive or histological outcomes. PMID:25911580

  17. Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

    DEFF Research Database (Denmark)

    Jensen, Vivi F. H.; Molck, Anne-Marie; Chapman, Melissa

    2017-01-01

    of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different...... substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain......The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels...

  18. Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

    Science.gov (United States)

    Yang, Feng-Yi; Chang, Wen-Yuan; Chen, Jyh-Cheng; Lee, Lin-Chien; Hung, Yi-Shun

    2014-04-15

    The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Glucose consumption of inflammatory cells masks metabolic deficits in the brain.

    Science.gov (United States)

    Backes, Heiko; Walberer, Maureen; Ladwig, Anne; Rueger, Maria A; Neumaier, Bernd; Endepols, Heike; Hoehn, Mathias; Fink, Gereon R; Schroeter, Michael; Graf, Rudolf

    2016-03-01

    Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Heat shock protein 70 modulates neural progenitor cells dynamics in human neuroblastoma SH-SY5Y cells exposed to high glucose content.

    Science.gov (United States)

    Salimi, Leila; Rahbarghazi, Reza; Jafarian, Vahab; Biray Avci, Çıgır; Goker Bagca, Bakiye; Pinar Ozates, Neslihan; Khaksar, Majid; Nourazarian, Alireza

    2018-01-18

    In the current experiment, detrimental effects of high glucose condition were investigated on human neuroblastoma cells. Human neuroblastoma cell line SH-SY5Y were exposed to 5, 40, and 70 mM glucose over a period of 72 h. Survival rate and the proliferation of cells were analyzed by MTT and BrdU incorporation assays. Apoptosis was studied by the assays of flow cytometry and PCR array. In order to investigate the trans-differentiation capacity of the cell into mature neurons, we used immunofluorescence imaging to follow NeuN protein level. The transcription level of HSP70 was shown by real-time PCR analysis. MMP-2 and -9 activities were shown by gelatin Zymography. According to data from MTT and BrdU incorporation assay, 70 mM glucose reduced cell viability and proliferation rate as compared to control (5 mM glucose) and cells treated with 40 mM glucose (P Cell exposure to 70 mM glucose had potential to induced apoptosis after 72 h (P SH-SY5Y cells to detrimental effects of high glucose condition during trans-differentiation into mature neuron-like cells. Real-time PCR analysis confirmed the expression of HSP70 in cells under high content glucose levels, demonstrating the possible cell compensatory response to an insulting condition (p control vs 70 mM group  cells being exposed to 70 mM glucose. High glucose condition could abrogate the dynamics of neural progenitor cells. The intracellular level of HSP70 was proportional to cell damage in high glucose condition. © 2018 Wiley Periodicals, Inc.

  1. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  2. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  3. Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation.

    Science.gov (United States)

    Wei, Wenjie; Yu, Zhiyuan; Xie, Minjie; Wang, Wei; Luo, Xiang

    2017-01-01

    Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD-induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase.

  4. Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

    Science.gov (United States)

    Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

    2016-01-01

    Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

  5. Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation.

    Science.gov (United States)

    Du, Yang; Deng, Wenjun; Wang, Zixing; Ning, MingMing; Zhang, Wei; Zhou, Yiming; Lo, Eng H; Xing, Changhong

    2017-04-01

    Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

  6. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    Science.gov (United States)

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  7. Time series changes of MR/PET image of brain glucose metabolism in healthy subjects and alzheimer disease patients

    International Nuclear Information System (INIS)

    Tarusawa, Ayaka; Nihei, Mitsuyo; Tanaka, Mika; Fukami, Tadanori; Yuasa, Tetsuya; Wu, Jin; Kawasaki, Keiichi; Ishiwata, Kiichi; Ishii, Kenji

    2010-01-01

    Combination of morphological information by MRI and functional one by positron emission tomography (PET) was applied to quantitative evaluation of brain regional glucose metabolism in healthy subjects (HS) and Alzheimer disease patients (AD) and their individual aging changes were elucidated for ultimate purpose of computer-aided diagnosis. Subjects were: 5 AD patients (3M/2F, av. age 77.27 y), 14 ε4-carrying HS (EHS, 4M/10F, 71.3y) and 24 non-ε4-carrying HS (NEHS, 4M/20F, 70.21), where ε4 (apolipoprotein E type 4 gene allele)-carrying HS were reported to be prone to early AD and to tend to give increased brain atrophy incidence. Acquisitions of T1-weighted 3D MR and PET images were in 256 x 256 x(88-104) and x (90-100) voxels, respectively, with digitization level 16 bits, and were repeated 3 times in the time series of 21-38 months. Segmentation was performed with the MR imaging software SPM8 (Statistic Parametric Mapping: Metalab) to specify the regions of white/gray matters and cerebrospinal fluid (CSF). The binary MR and registered PET images were fused for comparison of glucose metabolism by SUVs (standardized uptake values) in gray matter of the three subject groups. Findings were: SUV in AD was markedly reduced; average time series changes per year were 0.11% in AD, -2.63% in EHS and 1.48% in NEHS; and statistical significance of the changes was between AD and NEHS, and between EHS and NEHS. Glucose metabolism by MR/PET can be thus used for a distinction of ε4-carrier and non-carrier in HS. (T.T.)

  8. Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

    Directory of Open Access Journals (Sweden)

    Vivi F. H. Jensen

    2017-01-01

    Full Text Available The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls. The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

  9. Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

    Science.gov (United States)

    Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

    2017-01-01

    The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

  10. Comments on "Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Mental Retardation and Down Syndrome."

    Science.gov (United States)

    Willerman, Lee; Schultz, Robert T.

    1995-01-01

    The relationship between mental retardation and brain size is discussed. Research suggests that a common path for many otherwise idiopathic mild retardation cases (genetic or environmental) could be small brain size, indicating reduced information processing capacity. Suggestions are made for further research on neuron number. (SLD)

  11. To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS

    Science.gov (United States)

    Göbl, Christian S.; Ott, Johannes; Bozkurt, Latife; Feichtinger, Michael; Rehmann, Victoria; Cserjan, Anna; Heinisch, Maike; Steinbrecher, Helmut; JustKukurova, Ivica; Tuskova, Radka; Leutner, Michael; Vytiska-Binstorfer, Elisabeth; Kurz, Christine; Weghofer, Andrea; Tura, Andrea; Egarter, Christian; Kautzky-Willer, Alexandra

    2016-01-01

    Aims There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. Methods A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Results Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Conclusions Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile. PMID:27505055

  12. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  13. Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  14. Influence of Glucose Deprivation on Membrane Potentials of Plasma Membranes, Mitochondria and Synaptic Vesicles in Rat Brain Synaptosomes.

    Science.gov (United States)

    Hrynevich, Sviatlana V; Pekun, Tatyana G; Waseem, Tatyana V; Fedorovich, Sergei V

    2015-06-01

    Hypoglycemia can cause neuronal cell death similar to that of glutamate-induced cell death. In the present paper, we investigated the effect of glucose removal from incubation medium on changes of mitochondrial and plasma membrane potentials in rat brain synaptosomes using the fluorescent dyes DiSC3(5) and JC-1. We also monitored pH gradients in synaptic vesicles and their recycling by the fluorescent dye acridine orange. Glucose deprivation was found to cause an inhibition of K(+)-induced Ca(2+)-dependent exocytosis and a shift of mitochondrial and plasma membrane potentials to more positive values. The sensitivity of these parameters to the energy deficit caused by the removal of glucose showed the following order: mitochondrial membrane potential > plasma membrane potential > pH gradient in synaptic vesicles. The latter was almost unaffected by deprivation compared with the control. The pH-dependent dye acridine orange was used to investigate synaptic vesicle recycling. However, the compound's fluorescence was shown to be enhanced also by the mixture of mitochondrial toxins rotenone (10 µM) and oligomycin (5 µg/mL). This means that acridine orange can presumably be partially distributed in the intermembrane space of mitochondria. Glucose removal from the incubation medium resulted in a 3.7-fold raise of acridine orange response to rotenone + oligomycin suggesting a dramatic increase in the mitochondrial pH gradient. Our results suggest that the biophysical characteristics of neuronal presynaptic endings do not favor excessive non-controlled neurotransmitter release in case of hypoglycemia. The inhibition of exocytosis and the increase of the mitochondrial pH gradient, while preserving the vesicular pH gradient, are proposed as compensatory mechanisms.

  15. Glucose concentrations modulate brain-derived neurotrophic factor responsiveness of neurones in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    McIsaac, W; Ferguson, A V

    2017-04-01

    The hypothalamic paraventricular nucleus (PVN) is critical for normal energy balance and has been shown to contain high levels of both brain-derived neurotrophic factor (BDNF) and tropomyosin-receptor kinase B mRNA. Microinjections of BDNF into the PVN increase energy expenditure, suggesting that BDNF plays an important role in energy homeostasis through direct actions in this nucleus. The present study aimed to examine the postsynaptic effects of BDNF on the membrane potential of PVN neurones, and also to determine whether extracellular glucose concentrations modulated these effects. We used hypothalamic PVN slices from male Sprague-Dawley rats to perform whole cell current-clamp recordings from PVN neurones. BDNF was bath applied at a concentration of 2 nmol L -1 and the effects on membrane potential determined. BDNF caused depolarisations in 54% of neurones (n=25; mean±SEM, 8.9±1.2 mV) and hyperpolarisations in 23% (n=11; -6.7±1.4 mV), whereas the remaining cells were unaffected. These effects were maintained in the presence of tetrodotoxin (n=9; 56% depolarised, 22% hyperpolarised, 22% nonresponders), or the GABA a antagonist bicuculline (n=12; 42% depolarised, 17% hyperpolarised, 41% nonresponders), supporting the conclusion that these effects on membrane potential were postsynaptic. Current-clamp recordings from PVN neurones next examined the effects of BDNF on these neurones at varying extracellular glucose concentrations. Larger proportions of PVN neurones hyperpolarised in response to BDNF as the glucose concentrations decreased [10 mmol L -1 glucose 23% (n=11) of neurones hyperpolarised, whereas, at 0.2 mmol L -1 glucose, 71% showed hyperpolarising effects (n=12)]. Our findings reveal that BDNF has direct GABA A independent effects on PVN neurones, which are modulated by local glucose concentrations. The latter observation further emphasises the critical importance of using physiologically relevant conditions in an investigation of the central

  16. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

    Science.gov (United States)

    Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

    2014-12-01

    Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Utilization of D-beta-hydroxybutyrate and oleate as alternate energy fuels in brain cell cultures of newborn mice after hypoxia at different glucose concentrations.

    Science.gov (United States)

    Bossi, E; Kohler, E; Herschkowitz, N

    1989-11-01

    In dissociated whole brain cell cultures from newborn mice, we have previously shown that during glucose deprivation under normoxia, D-beta-hydroxybutyrate and oleic acid are increasingly used for energy production. We now asked whether this glucose dependency of the utilization of D-beta-hydroxybutyrate and oleic acid as alternate energy fuels is also present after a hypoxic phase. 3-Hydroxy[3-14C]butyrate or [U-14C]oleic acid were added to 7- and 14-d-old cultures and 14CO2-production compared after hypoxia in normal and glucose-deprived conditions. After hypoxia, the ability of the cells 7 d in culture to increase D-beta-hydroxybutyrate consumption in response to glucose deprivation is diminished, 14-d-old cells lose this ability. In contrast, after hypoxia, both 7- and 14-d-old cultures maintain or even improve the ability to increase oleate consumption, when glucose is lacking.

  18. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

    Science.gov (United States)

    Marin-Valencia, Isaac; Good, Levi B; Ma, Qian; Malloy, Craig R; Pascual, Juan M

    2013-01-01

    It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-13C3]heptanoate was examined in the normal mouse brain and in G1D by 13C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in 13C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and 13C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. PMID:23072752

  19. Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.

    Science.gov (United States)

    Hyder, Fahmeed; Herman, Peter; Bailey, Christopher J; Møller, Arne; Globinsky, Ronen; Fulbright, Robert K; Rothman, Douglas L; Gjedde, Albert

    2016-05-01

    Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements. © The Author(s) 2016.

  20. Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

    Directory of Open Access Journals (Sweden)

    June Zhou

    2017-09-01

    Full Text Available Traumatic brain injury (TBI causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group underwent sham or unilateral controlled cortical impact (CCI injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1 mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK 1, pyruvate kinase, and pyruvate dehydrogenase (PDH] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2 capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3 astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4 HK2 (an isoform of hexokinase expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific

  1. Microdialysis combined blood sampling technique for the determination of rosiglitazone and glucose in brain and blood of gerbils subjected to cerebral ischemia.

    Science.gov (United States)

    Sheu, Wayne H-H; Chuang, Hsiu-Chun; Cheng, Shiu-Min; Lee, Maw-Rong; Chou, Chi-Chi; Cheng, Fu-Chou

    2011-03-25

    Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (pblood glucose levels to 80% at 1h after pretreatment of rosiglitazone (pglucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose.

    Science.gov (United States)

    Gejl, Michael; Rungby, Jørgen; Brock, Birgitte; Gjedde, Albert

    2014-08-01

    Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP-1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP-1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP-1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre-clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady-state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose transfer and metabolism. This MiniReview examines the potential of GLP-1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis-Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP-1 receptor activation on blood-brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. Regional registration of [6-14C]glucose metabolism during brain activation of α-syntrophin knockout mice

    Science.gov (United States)

    Cruz, Nancy F.; Ball, Kelly K.; Froehner, Stanley C.; Adams, Marvin E.; Dienel, Gerald A.

    2013-01-01

    α-Syntrophin is a component of the dystrophin scaffold-protein complex that serves as an adaptor for recruitment of key proteins to the cytoplasmic side of plasma membranes. α-Syntrophin knockout (KO) causes loss of the polarized localization of aquaporin4 (AQP4) at astrocytic endfeet and interferes with water and K+ homeostasis. During brain activation, release of ions and metabolites from endfeet is anticipated to increase perivascular fluid osmolarity, AQP4-mediated osmotic water flow from endfeet, and metabolite washout from brain. This study tests the hypothesis that reduced levels of endfoot AQP4 increase retention of [14C]metabolites during sensory stimulation. Conscious KO and wildtype mice were pulse-labeled with [6-14C]glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [14C]metabolites in extracts, respectively. High-resolution autoradiographic assays detected a 17% side-to-side difference (P<0.05) in inferior colliculus of KO mice, not wildtype mice. However, there were no labeling differences between KO and wildtype mice for five major HPLC fractions from four dissected regions, presumably due to insufficient anatomical resolution. The results suggest a role for AQP4-mediated water flow in support of washout of metabolites, and underscore the need for greater understanding of astrocytic water and metabolite fluxes. PMID:23346911

  4. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-13C2 glucose

    Science.gov (United States)

    Jalloh, Ibrahim; Carpenter, Keri L H; Grice, Peter; Howe, Duncan J; Mason, Andrew; Gallagher, Clare N; Helmy, Adel; Murphy, Michael P; Menon, David K; Carpenter, T Adrian; Pickard, John D; Hutchinson, Peter J

    2015-01-01

    Increased ‘anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-13C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. 13C enrichment for glycolytic 2,3-13C2 lactate was the median 5.4% (interquartile range (IQR) 4.6–7.5%) in TBI brain and 4.2% (2.4–4.4%) in ‘normal' brain (Pbrain and 6.7% (6.3–8.9%) in ‘normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=−0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than ‘normal' brain. Several TBI patients exhibited PPP–lactate elevation above the ‘normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain. PMID:25335801

  5. Glucose transporter 1 and monocarboxylate transporters 1, 2, and 4 localization within the glial cells of shark blood-brain-barriers.

    Directory of Open Access Journals (Sweden)

    Carolina Balmaceda-Aguilera

    Full Text Available Although previous studies showed that glucose is used to support the metabolic activity of the cartilaginous fish brain, the distribution and expression levels of glucose transporter (GLUT isoforms remained undetermined. Optic/ultrastructural immunohistochemistry approaches were used to determine the expression of GLUT1 in the glial blood-brain barrier (gBBB. GLUT1 was observed solely in glial cells; it was primarily located in end-feet processes of the gBBB. Western blot analysis showed a protein with a molecular mass of 50 kDa, and partial sequencing confirmed GLUT1 identity. Similar approaches were used to demonstrate increased GLUT1 polarization to both apical and basolateral membranes in choroid plexus epithelial cells. To explore monocarboxylate transporter (MCT involvement in shark brain metabolism, the expression of MCTs was analyzed. MCT1, 2 and 4 were expressed in endothelial cells; however, only MCT1 and MCT4 were present in glial cells. In neurons, MCT2 was localized at the cell membrane whereas MCT1 was detected within mitochondria. Previous studies demonstrated that hypoxia modified GLUT and MCT expression in mammalian brain cells, which was mediated by the transcription factor, hypoxia inducible factor-1. Similarly, we observed that hypoxia modified MCT1 cellular distribution and MCT4 expression in shark telencephalic area and brain stem, confirming the role of these transporters in hypoxia adaptation. Finally, using three-dimensional ultrastructural microscopy, the interaction between glial end-feet and leaky blood vessels of shark brain was assessed in the present study. These data suggested that the brains of shark may take up glucose from blood using a different mechanism than that used by mammalian brains, which may induce astrocyte-neuron lactate shuttling and metabolic coupling as observed in mammalian brain. Our data suggested that the structural conditions and expression patterns of GLUT1, MCT1, MCT2 and MCT4 in shark

  6. The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

    Science.gov (United States)

    Dienel, Gerald A

    2017-01-10

    Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    Energy Technology Data Exchange (ETDEWEB)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

    2009-07-15

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  8. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    International Nuclear Information System (INIS)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

    2009-01-01

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  9. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

    Science.gov (United States)

    Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2014-05-01

    Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  10. Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid Chemoreceptor (CChr) Stimulation in Rats.

    Science.gov (United States)

    Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Dobrovinskaya, O; Melnikov, V; Lemus, M; de Álvarez-Buylla, E Roces

    2015-01-01

    Glutamate, released from central terminals of glossopharyngeal nerve, is a major excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS) afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA antagonist) into the cNTS before carotid chemoreceptor stimulation in anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3 receptor and c-Fos protein expressions in cNTS neurons were determined. We showed that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF group. In contrast, NBQX in similar conditions, did not modify the effects on glucose variables observed in aCSF control group. These experiments suggest that glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in glucose homeostasis.

  11. Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects

    Directory of Open Access Journals (Sweden)

    Shuai Liu

    2018-01-01

    Full Text Available Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

  12. Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

    Science.gov (United States)

    Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

    2016-03-01

    Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

  13. Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

    International Nuclear Information System (INIS)

    Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

    2016-01-01

    Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology. (paper)

  14. Postnatal development of EEG patterns, catecholamine contents and myelination, and effect of hyperthyroidism in Suncus brain.

    Science.gov (United States)

    Takeuchi, T; Sitizyo, K; Harada, E

    1998-03-01

    The postnatal development of the central nervous system (CNS) in house musk shrew in the early stage of maturation was studied. The electroencephalogram (EEG) and visual evoked potential (VEP) in association with catecholamine contents and myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the 20th day of postnatal age. Different EEG patterns which were specific to behavioral states (awake and drowsy) were first recorded on the 5th day, and the total power which was obtained by power spectrum analysis increased after this stage. The latencies of all peaks in VEP markedly shortened between the 5th and the 7th day. Noradrenalin (NA) content of the brain showed a slight increase after the 3rd day, and reached maximum levels on the 7th day, which was delayed a few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon occurred from the 7th to the 10th day. These morphological changes in the brain advanced at the identical time-course to those in the electrophysiological development and increment of DA and NA contents.

  15. Effects of maternal exposure to trichloroethylene on glucose uptake and nucleic acid and protein levels in the brains of developing rat pups

    International Nuclear Information System (INIS)

    Gerbec, E.A.N.

    1985-01-01

    Trichloroethylene (TCE) is a widespread contaminant of drinking water sources. This study examined several biochemical aspects of the hippocampus and cerebellum of rat pups that were exposed prenatally (gestational) and postnatally (lactational) to TCE via their dams' drinking water. The effects of TCE on glucose uptake, and on nucleic and protein levels in brain tissue were examined in these pups. Glucose uptake in the cerebellum, hippocampus and whole brain of the pups during the first 21 days of life was measured using the tritium-labeled 2-deoxy-D-glucose (2-DG) dissection/scintillation counting technique. The author determined that 312 mg TCE/I in drinking water (total dam exposure was 684 mg) significantly depressed 2-DG uptake in the whole brains and cerebella of 7- to 21-day old pups. This concentration also reduced 2-DG uptake in the hippocampus of exposed pups at 7, 11, and 16 days, but the uptake returned to control levels by 21 days. No overt toxicity, such as lower body or brain weight, was observed at this exposure level. This decrease in 2-DG uptake is a reflection of a decreased relative glucose uptake in the TCE exposed animals. Total DNA and RNA were extracted and measured using a modification of the Schmidt-Thannhauser procedure and Schneider technique, respectively. Proteins were determined based on the method of Bradford (1976)

  16. Long-term exposure to high glucose induces changes in the content and distribution of some exocytotic proteins in cultured hippocampal neurons.

    Science.gov (United States)

    Gaspar, J M; Castilho, Á; Baptista, F I; Liberal, J; Ambrósio, A F

    2010-12-29

    A few studies have reported the existence of depletion of synaptic vesicles, and changes in neurotransmitter release and in the content of exocytotic proteins in the hippocampus of diabetic rats. Recently, we found that diabetes alters the levels of synaptic proteins in hippocampal nerve terminals. Hyperglycemia is considered the main trigger of diabetic complications, although other factors, such as low insulin levels, also contribute to diabetes-induced changes. Thus, the aim of this work was to evaluate whether long-term elevated glucose per se, which mimics prolonged hyperglycemia, induces significant changes in the content and localization of synaptic proteins involved in exocytosis in hippocampal neurons. Hippocampal cell cultures were cultured for 14 days and were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose), for 7 days. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. The protein levels of vesicle-associated membrane protein-2 (VAMP-2), synaptosomal-associated protein-25 (SNAP-25), syntaxin-1, synapsin-1, synaptophysin, synaptotagmin-1, rabphilin 3a, and also of vesicular glutamate and GABA transporters (VGluT-1 and VGAT), were evaluated by immunoblotting, and its localization was analyzed by immunocytochemistry. The majority of the proteins were not affected. However, elevated glucose decreased the content of SNAP-25 and increased the content of synaptotagmin-1 and VGluT-1. Moreover, there was an accumulation of syntaxin-1, synaptotagmin-1 and VGluT-1 in the cell body of some hippocampal neurons exposed to high glucose. No changes were detected in mannitol-treated cells. In conclusion, elevated glucose per se did not induce significant changes in the content of the majority of the synaptic proteins studied in hippocampal cultures, with the exception of SNAP-25, synaptotagmin-1 and VGluT-1. However, there was an accumulation of some proteins in cell bodies of hippocampal

  17. Effect of MgSO4 on the contents of Ca2+ in brain cell and NO in brain tissue of rats with radiation-induced acute brain injury

    International Nuclear Information System (INIS)

    Yuan Wenjia; Cui Fengmei; Liu Ping; He Chao; Tu Yu; Wang Lili

    2009-01-01

    The work is to explore the protection of magnesium sulfate(MgSO 4 ) on radiation-induced acute brain injury. Thirty six mature Sprague-Dawley(SD) rats were randomly divided into 3 groups of control, experimental control and experimental therapy group. The whole brains of SD rats of experimental control and experimental therapy group were irradiated with a dose of 20 Gy using 6 MeV electron beam. MgSO 4 was injected into the abdomen of experimental therapy rats group 1 day before, immediately and continue for 5 days after irradiation respectively. The brain tissues were taken on 3, 10, 17 and 24 d after irradiation. Ca 2+ content in brain cell was measured by laser scanning confocal microscopy, and the NO content in brain tissue was detected by the method of nitric acid reductase. Compared with the blank control group, the contents of Ca 2+ in brain cell and NO in brain tissue of the experimental control group increase (P 4 used in early stage can inhibit the contents of Ca 2+ in brain cell and NO in brain tissue after radiation-induced acute brain injury. It means that MgSO 4 has a protective effect on radiation-induced acute brain injury. (authors)

  18. Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance.

    Science.gov (United States)

    Kurabayashi, Atsushi; Tanaka, Chiharu; Matsumoto, Waka; Naganuma, Seiji; Furihata, Mutsuo; Inoue, Keiji; Kakinuma, Yoshihiko

    2018-05-01

    Our previous study revealed that cyclic hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Tritiated 2-deoxy-D-glucose: a high-resolution marker for autoradiographic localization of brain metabolism

    International Nuclear Information System (INIS)

    Hammer, R.P. Jr.; Herkenham, M.

    1984-01-01

    The technique for autoradiographic localization of 2-deoxy-D-glucose (2DG) uptake has become a useful method for observing alterations of functional brain activity resulting from experimental manipulation. Autoradiographic resolution is improved using tritiated ([3H]) rather than carbon-14 ([14C)]2DG, due to the lower energy and shorter path of tritium emissions. In addition, lower 2DG uptake by white matter relative to gray matter is exaggerated in the [3H]2DG autoradiographs due to the greater absorption of tritium emissions by lipids. Using [3H]2DG, it is possible to observe differential metabolic labeling in various individual nuclei or portions of nuclei that is unresolvable using [14C]2DG in the awake, normal animal. Heterogeneous patterns of 2DG uptake seen only with [3H]2DG are found in the nucleus accumbens, the anterior portion of the basolateral nucleus of the amygdala, specific nuclei of the inferior olivary complex, various hypothalamic regions, and a region straddling the border of the medial and lateral habenular nuclei. The lamination of differential 2DG uptake in the hippocampus is better localized using [3H]2DG. Autoradiographic resolution of labeled 2DG is further improved when the brain is perfused prior to frozen sectioning, due perhaps to selective fixation and retention of intracellular labeled 2-deoxy-glycogen. A series of [3H]2DG autoradiographs are presented together with views of the Nissl-stained sections that produced the autoradiographs

  20. Central control of glucose homeostasis: the brain--endocrine pancreas axis.

    Science.gov (United States)

    Thorens, B

    2010-10-01

    A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  1. miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

    Science.gov (United States)

    Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

    2017-01-01

    Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

  2. Daily Dose effect of Valerian root extract on some Neurotransmitter contents in different Brain areas of male Albino Rats

    International Nuclear Information System (INIS)

    Waggas, Abeer M

    2007-01-01

    The aim of the present study was to investigate the daily effect of valerian (Valeriana officinalis L .) root extract on epinephrine (E), norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) , and gamma-aminobutyric acid (GABA) contents in different brain areas (cerebellum , pons plus medulla oblongata , striatum , cerebral cortex, hypothalamus, midbrain and hippocampus) of male albino rats .The daily intraperitoneal ( i.p.) injection of 300 mg/kg body wt valerian for 30 days caused a significant increase in epinephrine ( E ) content in pons plus medulla oblongata, cerebral cortex , hypothalamus and in midbrain . Norepinephrine (NE ) content was significantly increased in all brain areas tested except in cerebellum and cerebral cortex . Dopamine (DA) content was significantly increased in all tested brain areas except in cerebral cortex and hippocampus . moreover , there was also a significant increase in serotonin (5-HT ) and 5-hydroxyindol acetic acid (5-HIAA) contents in all tested brain areas . However, gamma-aminobutyric acid (GABA) content was significantly decreased in all tested brain areas . After the extract withdrawal, the increase in ( E, NE, DA , 5-HT ) contents and the decrease in GABA content persisted in pons plus medulla oblongata , striatum , midbrain and hippocampus , and this might be due to regional differences toward the effect. The increase in E, NE, DA , 5-HT and 5-HIAA contents, at the same time the decrease in GABA content in the different brain areas of albino rats may be due to the presence of both valepotriates and valerenic acid in the extract which mediated the GABA ergic mechanisms including the inhibition of GABA metabolism and the increase in GABA synthesis and release , although agonized the GABAA receptors which led to the inhibit of the neurotransmitter release. Valerian root extract may be useful as a herbal medicine having sedative effect and it is safe. (author)

  3. NAD-content and metabolism in the mouse embryo and developing brain

    International Nuclear Information System (INIS)

    Beuningen, M. van; Streffer, C.; Beuningen, D. van

    1986-01-01

    Biochemical studies have shown that NAD is not only the coenzyme of dehydrogenase but also the substrate of poly-(ADPR)-synthetase which is involved in processes of cell proliferation and differentiation. The NAD and protein content was determined in the total embryo and in the CNS 9 to 13 days p.c. The embryos were X-irradiated 9 days p.c. The NAD content increased in the total mouse embryo during the early organogenesis. At the later period a decrease of the NAD content per mg protein was observed. This latter effect was apparently due to an increase of the NAD glycohydrolase activity. This enzyme degrades NAD. A similar development was observed in the developing mouse brain. However, the maximal NAD content per mg protein occurred on day 10 p.c. One of the enzyme activities, which are responsible for NAD synthesis, NMN-pyrophosphorylase, also increased in the brain at the same time. After the injection of C 14-nicotinamide, a precursor of NAD, it was observed that the radioactivity mainly appeared in nicotinamide and NAD. With progressing embryological development less nicotinamide was taken up by the embryonic tissue. When the embryos were X-irradiated on day 9 p.c. with 1.8 Gy the increase of NAD was considerably reduced during the next days, so that also the NAD level per mg protein was reduced. Also the NAD biosynthesis apparently decreased. This was shown again by the reduced NMN-pyrophosphorylase activity. The dose dependance of these effects was studied in the dose range 0.48-1.8 Gy. Two days p.r. most of the radiation effects were normalized again and at later periods even an overshoot of the enzyme activity was observed. The possible relevance of these effects for cell proliferation will be discussed. (orig.)

  4. Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.

    Science.gov (United States)

    Courchesne-Loyer, Alexandre; Croteau, Etienne; Castellano, Christian-Alexandre; St-Pierre, Valérie; Hennebelle, Marie; Cunnane, Stephen C

    2017-07-01

    Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11 C-AcAc and 18 F-fluorodeoxyglucose ( 18 F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12-24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

  5. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

    Science.gov (United States)

    Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

    2016-06-01

    Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

    Science.gov (United States)

    Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

    2014-06-20

    Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

  7. Energy and glucose pathways in thiamine deficient primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Ham, D; Karska-Wysocki, B

    2005-12-01

    Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

  8. Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

    Science.gov (United States)

    Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

    2015-05-01

    The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

  9. High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study.

    Directory of Open Access Journals (Sweden)

    Moyra E Mortby

    Full Text Available Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance.210 cognitively healthy individuals (68-73 years without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH study.Baseline blood glucose levels in the normal range (3.2-6.1 mmol/l were used to determine regional brain volumes and associated cognitive function at wave 3.Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus. Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men.These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.

  10. Relation of measured brain glucose utilisation and cerebral atrophy in man.

    Science.gov (United States)

    Schlageter, N L; Horwitz, B; Creasey, H; Carson, R; Duara, R; Berg, G W; Rapoport, S I

    1987-06-01

    The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.

  11. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

    International Nuclear Information System (INIS)

    Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi; Tsui, Wai H.; De Leon, Mony J.; Wang, Gene-Jack; Fowler, Joanna; Pupi, Alberto

    2007-01-01

    To examine CMRglc measures and corresponding glucose transport (K 1 and k 2 ) and phosphorylation (k 3 ) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 ± 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 ± 9 years, three females, median MMSE 30). Absolute CMRglc (μmol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k 3 reductions were found in the hippocampus, PCC and amygdala. K 1 reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

  12. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    International Nuclear Information System (INIS)

    Kasalicky, J.; Konopkova, M.; Melichar, F.

    2001-01-01

    To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  13. Glucose administration after traumatic brain injury exerts some benefits and no adverse effects on behavioral and histological outcomes.

    Science.gov (United States)

    Shijo, Katsunori; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2015-07-21

    The impact of hyperglycemia after traumatic brain injury (TBI), and even the administration of glucose-containing solutions to head injured patients, remains controversial. In the current study adult male Sprague-Dawley rats were tested on behavioral tasks and then underwent surgery to induce sham injury or unilateral controlled cortical impact (CCI) injury followed by injections (i.p.) with either a 50% glucose solution (Glc; 2g/kg) or an equivalent volume of either 0.9% or 8% saline (Sal) at 0, 1, 3 and 6h post-injury. The type of saline treatment did not significantly affect any outcome measures, so these data were combined. Rats with CCI had significant deficits in beam-walking traversal time and rating scores (p's beam-walking deficits were not affected by Glc versus Sal treatments. Persistent post-CCI deficits in forelimb contraflexion scores and forelimb tactile placing ability were also not differentially affected by Glc or Sal treatments. However, deficits in latency to retract the right hind limb after limb extension were significantly attenuated in the CCI-Glc group (p < 0.05 versus CCI-Sal). Both CCI groups were significantly impaired in a plus maze test of spatial working memory on days 4, 9 and 14 post-surgery (p < 0.001 versus sham), and there was no effect of Glc versus Sal on this cognitive outcome measure. At 15 days post-surgery the loss of cortical tissue volume (p < 0.001 versus sham) was significantly less in the CCI-Glc group (30.0%; p < 0.05) compared to the CCI-Sal group (35.7%). Counts of surviving hippocampal hilar neurons revealed a significant (~40%) loss ipsilateral to CCI (p < 0.001 versus sham), but neuronal loss in the hippocampus was not different in the CCI-Sal and CCI-Glc groups. Taken together, these results indicate that an early elevation of blood glucose may improve some neurological outcomes and, importantly, the induction of hyperglycemia after isolated TBI did not adversely affect any sensorimotor, cognitive or

  14. Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study

    Directory of Open Access Journals (Sweden)

    Akie Inami

    2017-01-01

    Full Text Available Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET. Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT intervention (treatment condition and once after resting (control condition. We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity, and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

  15. Reduction in cardiolipin decreases mitochondrial spare respiratory capacity and increases glucose transport into and across human brain cerebral microvascular endothelial cells.

    Science.gov (United States)

    Nguyen, Hieu M; Mejia, Edgard M; Chang, Wenguang; Wang, Ying; Watson, Emily; On, Ngoc; Miller, Donald W; Hatch, Grant M

    2016-10-01

    Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin is a mitochondrial phospholipid required for function of the electron transport chain and ATP generation. We examined the role of cardiolipin in maintaining mitochondrial function necessary to support barrier properties of brain microvessel endothelial cells. Knockdown of the terminal enzyme of cardiolipin synthesis, cardiolipin synthase, in hCMEC/D3 cells resulted in decreased cellular cardiolipin levels compared to controls. The reduction in cardiolipin resulted in decreased mitochondrial spare respiratory capacity, increased pyruvate kinase activity, and increased 2-deoxy-[(3) H]glucose uptake and glucose transporter-1 expression and localization to membranes in hCMEC/D3 cells compared to controls. The mechanism for the increase in glucose uptake was an increase in adenosine-5'-monophosphate kinase and protein kinase B activity and decreased glycogen synthase kinase 3 beta activity. Knockdown of cardiolipin synthase did not affect permeability of fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell(®) inserts. In contrast, knockdown of cardiolipin synthase resulted in an increase in 2-deoxy-[(3) H]glucose transport across these monolayers compared to controls. The data indicate that in hCMEC/D3 cells, spare respiratory capacity is dependent on cardiolipin. In addition, reduction in cardiolipin in these cells alters their cellular energy status and this results in increased glucose transport into and across hCMEC/D3 monolayers. Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. In human adult brain endothelial cell hCMEC/D3 monolayers cultured on Transwell(®) plates, knockdown of cardiolipin synthase results in decrease in mitochondrial

  16. Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

    Science.gov (United States)

    Haugstad, T S; Valø, E T; Langmoen, I A

    1995-12-01

    The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

  17. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    Science.gov (United States)

    Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

    2017-02-01

    It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

  18. Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

    Science.gov (United States)

    Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

    2016-01-01

    A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

  19. The use of glucose oxidase and catalase for the enzymatic reduction of the potential ethanol content in wine.

    Science.gov (United States)

    Röcker, Jessica; Schmitt, Matthias; Pasch, Ludwig; Ebert, Kristin; Grossmann, Manfred

    2016-11-01

    Due to the increase of sugar levels in wine grapes as one of the impacts of climate change, alcohol reduction in wines becomes a major focus of interest. This study combines the use of glucose oxidase and catalase activities with the aim of rapid conversion of glucose into non-fermentable gluconic acid. The H2O2 hydrolysing activity of purified catalase is necessary in order to stabilize glucose oxidase activity. After establishing the adequate enzyme ratio, the procedure was applied in large-scale trials (16L- and 220L-scale) of which one was conducted in a winery under industrial wine making conditions. Both enzyme activity and wine flavour were clearly influenced by the obligatory aeration in the different trials. With the enzyme treatment an alcohol reduction of 2%vol. was achieved after 30h of aeration. However the enzyme treated wines were significantly more acidic and less typical. Copyright © 2016. Published by Elsevier Ltd.

  20. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  1. Content

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    secondary levels. In subject matter didactics, the question of content is more developed, but it is still mostly confined to teaching on lower levels. As for higher education didactics, discussions on selection of content are almost non-existent on the programmatic level. Nevertheless, teachers are forced...... curriculum, in higher education, and to generate analytical categories and criteria for selection of content, which can be used for systematic didactical reflection. The larger project also concerns reflection on and clarification of the concept of content, including the relation between content at the level......Aim, content and methods are fundamental categories of both theoretical and practical general didactics. A quick glance in recent pedagogical literature on higher education, however, reveals a strong preoccupation with methods, i.e. how teaching should be organized socially (Biggs & Tang, 2007...

  2. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    International Nuclear Information System (INIS)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki

    2009-01-01

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6±18.2 years; 46 females, mean age 40.6±19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  3. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  4. Rapid decrease in brain enkephalin content after low-dose whole-body X-irradiation of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Miyachi, Yukihisa (Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.); Ogawa, Norio; Mori, Akitane

    1992-03-01

    Methionine-eckephalin (ME) contents in the hypothalamus and other rat brain structures were measured immediately after 10 or 20 cGy whole-body X-irradiation. The ME contents of homogenates of the striatum, hypothalamus, midbrain + thalamus, hindbrain and pituitary were assayed radioimmunologically with {sup 125}I. The contents of all the structure, except the pituitary, decreased significantly after 20 cGy irradiation. The reduction in the hypothalamus was transient, ME content gradually recovering with time. These results suggest that the central nervous system of mammals is one of the most radiosensitive organs as judged by changes in stress-induced mediators such as ME. (author).

  5. Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye

    2017-01-01

    brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for51Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure......, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB...

  6. Bisphenol A disrupts glucose transport and neurophysiological role of IR/IRS/AKT/GSK3β axis in the brain of male mice.

    Science.gov (United States)

    Li, Jing; Wang, Yixin; Fang, Fangfang; Chen, Donglong; Gao, Yue; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2016-04-01

    Bisphenol A (BPA), one of the most prevalent chemicals for daily use, was recently reported to disturb the homeostasis of energy metabolism and insulin signaling pathways, which might contribute to the increasing prevalence rate of mild cognitive impairment (MCI). However, the underlying mechanisms are remained poorly understood. Here we studied the effects of low dose BPA on glucose transport and the IR/IRS/AKT/GSK3β axis in adult male mice to delineate the association between insulin signaling disruption and neurotoxicity mediated by BPA. Mice were treated with subcutaneous injection of 100μg/kg/d BPA or vehicle for 30 days, then the insulin signaling and glucose transporters in the hippocampus and prefrontal cortex were detected by western blot. Our results showed that mice treated with BPA displayed significant decrease of insulin sensitivity, and in glucose transporter 1, 3 (GLUT1, 3) protein levels in mouse brain. Meanwhile, hyperactivation of IR/IRS/AKT/GSK3β axis was detected in the brain of BPA treated mice. Noteworthily, significant increases of phosphorylated tau and β-APP were observed in BPA treated mice. These results strongly suggest that BPA exposure significantly disrupts brain insulin signaling and might be considered as a potential risk factor for neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography

    International Nuclear Information System (INIS)

    Omata, N.; Fujibayashi, Y.; Waki, A.; Sadato, N.; Yano, R.; Yoshimoto, M.; Yonekura, Y.; Murata, T.; Yoshida, S.

    1999-01-01

    Fresh rat brain slices were incubated with 2-deoxy-2-[ 18 F]-fluoro-D-glucose ([ 18 F]FDG) in oxygenated Krebs-Ringer solution at 36 degree C, and serial two-dimensional time-resolved images of [ 18 F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [ 18 F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia ≤10-min, the k3* value returned to the pre-loading level. In contrast, with ≥20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues. (author)

  8. Metabolism of glucose in brain of patients with Parkinson's disease. Studies on /sup 11/C-glucose metabolism in the striatum and cerebral cortex during medication or interruption of medication by positron emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki

    1984-12-01

    We examined /sup 11/C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with /sup 11/C-Glucose (per os). /sup 11/C-Glucose was prepared from /sup 11/CO/sub 2/ by photosynthesis. 1) No significant difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author).

  9. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Park, Kwang Suk [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea); Seoul National University College of Medicine, Department of Biomedical Engineering, Seoul (Korea); Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul [Seoul National University College of Medicine, Department of Otolaryngology, Head and Neck Surgery, Seoul (Korea); Lee, Dong Soo; Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea)

    2005-06-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1-{sup 14}C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in

  10. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Park, Kwang Suk; Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul; Lee, Dong Soo; Jeong, Jae Min

    2005-01-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1- 14 C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in any

  11. Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

    Science.gov (United States)

    Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin

    2016-01-01

    Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789

  12. High-content screening of Aspergillus niger with both increased production and high secretion rate of glucose oxidase.

    Science.gov (United States)

    Zhu, Xudong; Sun, Jingchun; Chu, Ju

    2018-01-01

    To develop a rapid, dual-parameter, plate-based screening process to improve production and secretion rate of glucose oxidase simultaneously in Aspergillus niger. A morphology engineering based on CaCO 3 was implemented, where the yield of GOD by A. niger was increased by up to 50%. Analysis of extracellular GOD activity was achieved in 96-well plates. There was a close negative correlation between the total GOD activity and its residual glucose of the fermentation broth. Based on this, a rapid, plate-based, qualitative analysis method of the total GOD activity was developed. Compared with the conventional analysis method using o-dianisidine, a correlation coefficient of -0.92 by statistical analysis was obtained. Using this dual-parameter screening method, we acquired a strain with GOD activity of 3126 U l -1 , which was 146% higher than the original strain. Its secretion rate of GOD was 83, 32% higher than the original strain.

  13. Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain.

    Science.gov (United States)

    Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F; Gore, John C; Smith, Seth A

    2018-03-24

    To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T. SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (t I/ t D ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R 1 of free water (R 1f ), and the rate of MT exchange (k mf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal t I /t D combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient. Two optimal sampling schemes were determined: (i) a 5-point scheme (k mf estimated) and (ii) a 4-point scheme (k mf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing k mf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain. qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB 0 , B1+, and T 1 ) when optimized t I -t D combinations are selected. © 2018 International Society for Magnetic Resonance in Medicine.

  14. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

    Science.gov (United States)

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-01-01

    NAD is an essential metabolite that exists in NAD+ or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+ and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ. PMID:25730862

  15. A positron emission tomography analysis of glucose metabolism in Alzheimer's disease brain using [18F] fluorodeoxyglucose. A parallel study with elemental concentrations

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.; Stedman, J.D.

    2000-01-01

    Alzheimer's disease (AD) is a debilitating form of dementia which leads to impaired memory, thinking and behavior. Elemental concentrations between 'normal' and AD subjects as well as the hemispherical differences within the brain were examined. Tissue samples from both hemispheres of the frontal lobe in both AD and normal subjects were examined for their trace element concentrations using PIXE and RBS analyses. Elemental concentrations were seen to differ between AD and normal brain tissue samples. While in the normal group concentrations were found to be significantly higher in the right hemisphere than in the left the converse was tru in AD. A change in elemental concentrations may indicate possible alterations in the function of the blood brain barrier. This was examined by determining regional cerebral metabolic rates of glucose (rCMRGlu) using the in vivo technique of positron emission tomography (PET). Again variations between both hemispheres and between AD and normal were found. (author)

  16. Determining the Feasibility, Content Validity, and Internal Consistency of a Newly Developed Care Coordination Scale for People with Brain Injury

    Directory of Open Access Journals (Sweden)

    Brian P. Johnson

    2017-07-01

    Full Text Available Background: With the increasing complexity of care, people with disabilities and supportive significant others (SSO must often coordinate key aspects of their own care, but no validated scale currently exists to comprehensively characterize the activities done to manage and coordinate their care. Method: This study aimed to improve the feasibility, acceptability, and content validity of the Care and Service Coordination and Management (CASCAM scale and to test its internal consistency. Questionnaire items were administered to 23 individuals with acquired brain injury and 17 SSO. Results: Respondents confirmed content validity and that the instrument addresses important care coordination and management issues. The internal consistency of care coordination domains for medical/ rehabilitative and independent living needs for people with brain injury and their SSO ranged from α = .774 to .945. Conclusion: Care coordination activities by persons with disabilities, including brain injury, and their SSO are multifaceted but feasibly measurable and should be assessed to improve care.

  17. Consistency and Variation in School-Level Youth Sports Traumatic Brain Injury Policy Content.

    Science.gov (United States)

    Coxe, Kathryn; Hamilton, Kelsey; Harvey, Hosea H; Xiang, Joe; Ramirez, Marizen R; Yang, Jingzhen

    2018-03-01

    The purpose of the study was to examine the consistency and variation in content of high school written traumatic brain injury (TBI) policies in relation to the three key tenets of youth sports TBI laws. A content analysis was conducted on written TBI policies retrieved from 71 high schools currently participating in High School Reporting Information Online. Each policy was independently analyzed by two trained coders. The number and percent of the policies reflecting the three key tenets of state youth sports TBI laws were described and compared on policy enforcement (i.e., strictness of language), policy description (i.e., details and definitions of the requirements), and policy implementation steps (i.e., specific steps for implementing the requirements). Direct quotes were identified to support quantitative findings. All 71 high school TBI policies contained at least two of the three main TBI law tenets, where 98.6% (n = 70) included the return to play tenet, 83.1% (n = 59) included the removal from play tenet, and 59.2% (n = 42) specified the distribution of TBI information sheets to student-athletes and their parents. Nearly half of the policies (49.3%, n = 35) required parents' signature while only 39.4% (n = 28) required students' signature on the TBI information sheet. The language exhibited wide variance across the 71 TBI policies regarding policy enforcement, policy description, and policy implementation specifications. All 71 TBI policies covered at least two of the three youth sports TBI law tenets, but with considerable variation. Future research should assess variations by schools within the same state and their impact on TBI rates in school athletics. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  18. The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

    Directory of Open Access Journals (Sweden)

    Desgagnés Julie

    2006-03-01

    Full Text Available Abstract Background Chlorogenic acid (CHL, the most potent functional inhibitor of the microsomal glucose-6-phosphate translocase (G6PT, is thought to possess cancer chemopreventive properties. It is not known, however, whether any G6PT functions are involved in tumorigenesis. We investigated the effects of CHL and the potential role of G6PT in regulating the invasive phenotype of brain tumor-derived glioma cells. Results RT-PCR was used to show that, among the adult and pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit glucose-6-phosphatase (G6Pase-α but expressed G6Pase-β which, when coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic tissues such as brain. CHL inhibited U-87 cell migration and matrix metalloproteinase (MMP-2 secretion, two prerequisites for tumor cell invasion. Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate (S1P, a potent mitogen for glioblastoma multiform cells, as well as the rapid, S1P-induced extracellular signal-regulated protein kinase phosphorylation potentially mediated through intracellular calcium mobilization, suggesting that G6PT may also perform crucial functions in regulating intracellular signalling. Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the adenosine triphosphate (ATP-depleting agents 2-deoxyglucose and 5-thioglucose, a mechanism that may inhibit ATP-mediated calcium sequestration by G6PT. Conclusion We illustrate a new G6PT function in glioma cells that could regulate the intracellular signalling and invasive phenotype of brain tumor cells, and that can be targeted by the anticancer properties of CHL.

  19. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...

  20. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    Directory of Open Access Journals (Sweden)

    Charlene eDiepenbroek

    2013-12-01

    Full Text Available Deep brain stimulation (DBS of the nucleus accumbens (NAc is an effective therapy for obsessive compulsive disorder (OCD and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of one hour. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

  1. TBIdoc: 3D content-based CT image retrieval system for traumatic brain injury

    Science.gov (United States)

    Li, Shimiao; Gong, Tianxia; Wang, Jie; Liu, Ruizhe; Tan, Chew Lim; Leong, Tze Yun; Pang, Boon Chuan; Lim, C. C. Tchoyoson; Lee, Cheng Kiang; Tian, Qi; Zhang, Zhuo

    2010-03-01

    Traumatic brain injury (TBI) is a major cause of death and disability. Computed Tomography (CT) scan is widely used in the diagnosis of TBI. Nowadays, large amount of TBI CT data is stacked in the hospital radiology department. Such data and the associated patient information contain valuable information for clinical diagnosis and outcome prediction. However, current hospital database system does not provide an efficient and intuitive tool for doctors to search out cases relevant to the current study case. In this paper, we present the TBIdoc system: a content-based image retrieval (CBIR) system which works on the TBI CT images. In this web-based system, user can query by uploading CT image slices from one study, retrieval result is a list of TBI cases ranked according to their 3D visual similarity to the query case. Specifically, cases of TBI CT images often present diffuse or focal lesions. In TBIdoc system, these pathological image features are represented as bin-based binary feature vectors. We use the Jaccard-Needham measure as the similarity measurement. Based on these, we propose a 3D similarity measure for computing the similarity score between two series of CT slices. nDCG is used to evaluate the system performance, which shows the system produces satisfactory retrieval results. The system is expected to improve the current hospital data management in TBI and to give better support for the clinical decision-making process. It may also contribute to the computer-aided education in TBI.

  2. Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

    Science.gov (United States)

    Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

    2017-01-01

    In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

  3. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    International Nuclear Information System (INIS)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2009-01-01

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  4. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    Energy Technology Data Exchange (ETDEWEB)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan); Fujitani, Yoshio, E-mail: fujitani@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan)

    2009-12-18

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  5. Honeybee glucose oxidase—its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys

    Science.gov (United States)

    Bucekova, Marcela; Valachova, Ivana; Kohutova, Lenka; Prochazka, Emanuel; Klaudiny, Jaroslav; Majtan, Juraj

    2014-08-01

    Antibacterial properties of honey largely depend on the accumulation of hydrogen peroxide (H2O2), which is generated by glucose oxidase (GOX)-mediated conversion of glucose in diluted honey. However, honeys exhibit considerable variation in their antibacterial activity. Therefore, the aim of the study was to identify the mechanism behind the variation in this activity and in the H2O2 content in honeys associated with the role of GOX in this process. Immunoblots and in situ hybridization analyses demonstrated that gox is solely expressed in the hypopharyngeal glands of worker bees performing various tasks and not in other glands or tissues. Real-time PCR with reference genes selected for worker heads shows that the gox expression progressively increases with ageing of the youngest bees and nurses and reached the highest values in processor bees. Immunoblot analysis of honey samples revealed that GOX is a regular honey component but its content significantly varied among honeys. Neither botanical source nor geographical origin of honeys affected the level of GOX suggesting that some other factors such as honeybee nutrition and/or genetic/epigenetic factors may take part in the observed variation. A strong correlation was found between the content of GOX and the level of generated H2O2 in honeys except honeydew honeys. Total antibacterial activity of most honey samples against Pseudomonas aeruginosa isolate significantly correlated with the H2O2 content. These results demonstrate that the level of GOX can significantly affect the total antibacterial activity of honey. They also support an idea that breeding of novel honeybee lines expressing higher amounts of GOX could help to increase the antibacterial efficacy of the hypopharyngeal gland secretion that could have positive influence on a resistance of colonies against bacterial pathogens.

  6. N-acetylcysteine is able to reduce the oxidation status and the endothelial activation after a high-glucose content meal in patients with Type 2 diabetes mellitus.

    Science.gov (United States)

    Masha, A; Brocato, L; Dinatale, S; Mascia, C; Biasi, F; Martina, V

    2009-04-01

    Post-prandial hyperglycemia seems to play a pivotal role in the pathogenesis of the cardiovascular complications of diabetes mellitus, as it leads to an oxidative stress which in turn causes a reduced NO bioavailability. These conditions produce an endothelial activation. The aim of this study was to assure that the administration of N-acetylcysteine (NAC), thiolic antioxidant, is able to decrease the oxidation status and endothelial activation after a high-glucose content meal. Ten patients with Type 2 diabetes mellitus (DMT2) (Group 1) and 10 normal subjects (Group 2) were studied. They assumed a high-glucose content meal without (phase A) or after (phase B) the administration of NAC. Glycemia, insulinemia, intercellular adhesion molecule 1, vascular adhesion molecule 1 (VCAM-1), E-selectin, malonaldehyde (MDA), and 4-hydroxynonenal (HNE) were assessed at -30, 0, +30, +60, +90, +120, and +180 min with respect to the meal consumption. During the phase A in Group 1, only HNE and MDA levels increased after the meal assumption; all parameters remained unchanged in Group 2. During the phase B, in Group 1, HNE, MDA, VCAM-1, and E-selectin levels after the meal were lower than those in phase A, while no change for all variables were observed in Group 2. A high-glucose meal produces an increase in oxidation parameters in patients with DMT2. The administration of NAC reduces the oxidative stress and, by doing so, reduces the endothelial activation. In conclusion, NAC could be efficacious in the slackening of the progression of vascular damage in DMT2.

  7. Glucose metabolism-weighted imaging with chemical exchange-sensitive MRI of 2-deoxyglucose (2DG) in brain: Sensitivity and biological sources.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2016-12-01

    Recent proof-of-principle studies have demonstrated the feasibility of measuring the uptake and metabolism of non-labeled 2-deoxy-D-glucose (2DG) by a chemical exchange-sensitive spin-lock (CESL) MRI approach. In order to gain better understanding of this new approach, we performed dynamic in vivo CESL MRI on healthy rat brains with an intravenous injection of 2DG under various conditions at 9.4T. For three 2DG doses of 0.25, 0.5 and 1g/kg, we found that 2DG-CESL signals increased linearly with injection dose at the initial (40min) suggesting time-dependent differential weightings of 2DG transport and metabolism. Remaining 2DG-CESL studies were performed with 0.25g/kg 2DG. Since a higher isoflurane level reduces glucose metabolism and increases blood flow, 2DG-CESL was measured under 0.5%, 1.5% and 2.2% isoflurane. The 2DG-CESL signal was reduced at higher isoflurane levels correlating well with the 2DG phosphorylation in the intracellular space. To detect regional heterogeneities of glucose metabolism, 2DG-CESL with 0.33×0.33×1.50mm 3 resolution was obtained, which indeed showed a higher response in the cortex compared to the corpus callosum. Lastly, unlike CESL MRI with the injection of non-transportable mannitol, the 2DG-CESL response decreased with an increased spin-lock pulse power confirming that 2DG-CESL is dominated by chemical exchange processes in the extravascular space. Taken together, our results showed that 2DG-CESL MRI signals mainly indicate glucose transport and metabolism and may be a useful biomarker for metabolic studies of normal and diseased brains. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Bravenboer, B.

    2004-01-01

    The brain has long been viewed as an insulin-insensitive organ. Following the demonstration of insulin receptors in the brain, this assumption has been challenged, and a whole new field of research has emerged. Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin

  9. The Sum of Its Parts—Effects of Gastric Distention, Nutrient Content and Sensory Stimulation on Brain Activation

    Science.gov (United States)

    Spetter, Maartje S.; de Graaf, Cees; Mars, Monica; Viergever, Max A.; Smeets, Paul A. M.

    2014-01-01

    During food consumption the brain integrates multiple interrelated neural and hormonal signals involved in the regulation of food intake. Factors influencing the decision to stop eating include the foods' sensory properties, macronutrient content, and volume, which in turn affect gastric distention and appetite hormone responses. So far, the contributions of gastric distention and oral stimulation by food on brain activation have not been studied. The primary objective of this study was to assess the effect of gastric distention with an intra-gastric load and the additional effect of oral stimulation on brain activity after food administration. Our secondary objective was to study the correlations between hormone responses and appetite-related ratings and brain activation. Fourteen men completed three functional magnetic resonance imaging sessions during which they either received a naso-gastric infusion of water (stomach distention), naso-gastric infusion of chocolate milk (stomach distention + nutrients), or ingested chocolate-milk (stomach distention + nutrients + oral exposure). Appetite ratings and blood parameters were measured at several time points. During gastric infusion, brain activation was observed in the midbrain, amygdala, hypothalamus, and hippocampus for both chocolate milk and water, i.e., irrespective of nutrient content. The thalamus, amygdala, putamen and precuneus were activated more after ingestion than after gastric infusion of chocolate milk, whereas infusion evoked greater activation in the hippocampus and anterior cingulate. Moreover, areas involved in gustation and reward were activated more after oral stimulation. Only insulin responses following naso-gastric infusion of chocolate milk correlated with brain activation, namely in the putamen and insula. In conclusion, we show that normal (oral) food ingestion evokes greater activation than gastric infusion in stomach distention and food intake-related brain areas. This provides neural

  10. The sum of its parts--effects of gastric distention, nutrient content and sensory stimulation on brain activation.

    Science.gov (United States)

    Spetter, Maartje S; de Graaf, Cees; Mars, Monica; Viergever, Max A; Smeets, Paul A M

    2014-01-01

    During food consumption the brain integrates multiple interrelated neural and hormonal signals involved in the regulation of food intake. Factors influencing the decision to stop eating include the foods' sensory properties, macronutrient content, and volume, which in turn affect gastric distention and appetite hormone responses. So far, the contributions of gastric distention and oral stimulation by food on brain activation have not been studied. The primary objective of this study was to assess the effect of gastric distention with an intra-gastric load and the additional effect of oral stimulation on brain activity after food administration. Our secondary objective was to study the correlations between hormone responses and appetite-related ratings and brain activation. Fourteen men completed three functional magnetic resonance imaging sessions during which they either received a naso-gastric infusion of water (stomach distention), naso-gastric infusion of chocolate milk (stomach distention + nutrients), or ingested chocolate-milk (stomach distention + nutrients + oral exposure). Appetite ratings and blood parameters were measured at several time points. During gastric infusion, brain activation was observed in the midbrain, amygdala, hypothalamus, and hippocampus for both chocolate milk and water, i.e., irrespective of nutrient content. The thalamus, amygdala, putamen and precuneus were activated more after ingestion than after gastric infusion of chocolate milk, whereas infusion evoked greater activation in the hippocampus and anterior cingulate. Moreover, areas involved in gustation and reward were activated more after oral stimulation. Only insulin responses following naso-gastric infusion of chocolate milk correlated with brain activation, namely in the putamen and insula. In conclusion, we show that normal (oral) food ingestion evokes greater activation than gastric infusion in stomach distention and food intake-related brain areas. This provides neural

  11. The sum of its parts--effects of gastric distention, nutrient content and sensory stimulation on brain activation.

    Directory of Open Access Journals (Sweden)

    Maartje S Spetter

    Full Text Available During food consumption the brain integrates multiple interrelated neural and hormonal signals involved in the regulation of food intake. Factors influencing the decision to stop eating include the foods' sensory properties, macronutrient content, and volume, which in turn affect gastric distention and appetite hormone responses. So far, the contributions of gastric distention and oral stimulation by food on brain activation have not been studied. The primary objective of this study was to assess the effect of gastric distention with an intra-gastric load and the additional effect of oral stimulation on brain activity after food administration. Our secondary objective was to study the correlations between hormone responses and appetite-related ratings and brain activation. Fourteen men completed three functional magnetic resonance imaging sessions during which they either received a naso-gastric infusion of water (stomach distention, naso-gastric infusion of chocolate milk (stomach distention + nutrients, or ingested chocolate-milk (stomach distention + nutrients + oral exposure. Appetite ratings and blood parameters were measured at several time points. During gastric infusion, brain activation was observed in the midbrain, amygdala, hypothalamus, and hippocampus for both chocolate milk and water, i.e., irrespective of nutrient content. The thalamus, amygdala, putamen and precuneus were activated more after ingestion than after gastric infusion of chocolate milk, whereas infusion evoked greater activation in the hippocampus and anterior cingulate. Moreover, areas involved in gustation and reward were activated more after oral stimulation. Only insulin responses following naso-gastric infusion of chocolate milk correlated with brain activation, namely in the putamen and insula. In conclusion, we show that normal (oral food ingestion evokes greater activation than gastric infusion in stomach distention and food intake-related brain areas. This

  12. Autonomic regulation of hepatic glucose production

    NARCIS (Netherlands)

    Bisschop, Peter H.; Fliers, Eric; Kalsbeek, Andries

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system

  13. Human ApoE Isoforms Differentially Modulate Glucose and Amyloid Metabolic Pathways in Female Brain: Evidence of the Mechanism of Neuroprotection by ApoE2 and Implications for Alzheimer's Disease Prevention and Early Intervention.

    Science.gov (United States)

    Keeney, Jeriel Thomas-Richard; Ibrahimi, Shaher; Zhao, Liqin

    2015-01-01

    Three major genetic isoforms of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4, exist in humans and lead to differences in susceptibility to Alzheimer's disease (AD). This study investigated the impact of human ApoE isoforms on brain metabolic pathways involved in glucose utilization and amyloid-β (Aβ) degradation, two major areas that are significantly perturbed in preclinical AD. Hippocampal RNA samples from middle-aged female mice with targeted human ApoE2, ApoE3, and ApoE4 gene replacement were comparatively analyzed with a qRT-PCR custom array for the expression of 85 genes involved in insulin/insulin-like growth factor (Igf) signaling. Consistent with its protective role against AD, ApoE2 brain exhibited the most metabolically robust profile among the three ApoE genotypes. When compared to ApoE2 brain, both ApoE3 and ApoE4 brains exhibited markedly reduced levels of Igf1, insulin receptor substrates (Irs), and facilitated glucose transporter 4 (Glut4), indicating reduced glucose uptake. Additionally, ApoE4 brain exhibited significantly decreased Pparg and insulin-degrading enzyme (Ide), indicating further compromised glucose metabolism and Aβ dysregulation associated with ApoE4. Protein analysis showed significantly decreased Igf1, Irs, and Glut4 in ApoE3 brain, and Igf1, Irs, Glut4, Pparg, and Ide in ApoE4 brain compared to ApoE2 brain. These data provide the first documented evidence that human ApoE isoforms differentially affect brain insulin/Igf signaling and downstream glucose and amyloid metabolic pathways, illustrating a potential mechanism for their differential risk in AD. A therapeutic strategy that enhances brain insulin/Igf1 signaling activity to a more robust ApoE2-like phenotype favoring both energy production and amyloid homeostasis holds promise for AD prevention and early intervention.

  14. What is the manner of gastric emptying after ingestion of liquids with differences in the volume under uniform glucose-based energy content?

    Science.gov (United States)

    Okabe, Tadashi; Terashima, Hideo; Sakamoto, Atsuhiro

    2017-10-01

    We previously demonstrated that the gastric emptying rate of liquids chiefly depended on the total amount of calories (energy content) in a uniform volume. The aim of the present study was to examine the effects of different volumes of liquids with a uniform energy content on gastric emptying. Three types of test solutions were prepared with a uniform amount of calories (200 kcal provided by glucose) and step-wise increments in volume (200 ml, 400 ml, and 600 ml). The gastric volume of each solution was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by 8 healthy volunteers. The mean gastric volume decreased exponentially to nearly 0 ml 70 min after ingestion in the 200 ml group, 90 min in the 400 ml group, and 100 min in the 600 ml group. Each gastric emptying curve converged with identical slopes on the graph when the points at which the gastric emptying curves of the 200 ml and 400 ml groups reached the zero point on the Y-axis (mean gastric volume) were shifted toward 110 min on the X-axis (time scale). The volume of liquid ingested with a uniform glucose-based energy content is a critical determinant of liquid gastric emptying. The gastric emptying time may be predicted following the ingestion of an isocaloric liquid with any volume over a predefined range once a gastric emptying curve following the ingestion of a liquid has been plotted on a graph. UMIN000014930. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Comparison of Glutamate Turnover in Nerve Terminals and Brain Tissue During [1,6-13C2]Glucose Metabolism in Anesthetized Rats.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam I M; Rothman, Douglas L; Behar, Kevin L

    2017-01-01

    The 13 C turnover of neurotransmitter amino acids (glutamate, GABA and aspartate) were determined from extracts of forebrain nerve terminals and brain homogenate, and fronto-parietal cortex from anesthetized rats undergoing timed infusions of [1,6- 13 C 2 ]glucose or [2- 13 C]acetate. Nerve terminal 13 C fractional labeling of glutamate and aspartate was lower than those in whole cortical tissue at all times measured (up to 120 min), suggesting either the presence of a constant dilution flux from an unlabeled substrate or an unlabeled (effectively non-communicating on the measurement timescale) glutamate pool in the nerve terminals. Half times of 13 C labeling from [1,6- 13 C 2 ]glucose, as estimated by least squares exponential fitting to the time course data, were longer for nerve terminals (Glu C4 , 21.8 min; GABA C2 21.0 min) compared to cortical tissue (Glu C4 , 12.4 min; GABA C2 , 14.5 min), except for Asp C3 , which was similar (26.5 vs. 27.0 min). The slower turnover of glutamate in the nerve terminals (but not GABA) compared to the cortex may reflect selective effects of anesthesia on activity-dependent glucose use, which might be more pronounced in the terminals. The 13 C labeling ratio for glutamate-C4 from [2- 13 C]acetate over that of 13 C-glucose was twice as large in nerve terminals compared to cortex, suggesting that astroglial glutamine under the 13 C glucose infusion was the likely source of much of the nerve terminal dilution. The net replenishment of most of the nerve terminal amino acid pools occurs directly via trafficking of astroglial glutamine.

  16. CSF glucose test

    Science.gov (United States)

    ... in the space surrounding the spinal cord and brain. ... Abnormal results include higher and lower glucose levels. Abnormal results may be due to: Infection (bacterial or fungus) Inflammation of the central nervous system Tumor

  17. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    International Nuclear Information System (INIS)

    Yamada, Akifumi; Momosaki, Sotaro; Hosoi, Rie; Abe, Kohji; Yamaguchi, Masatoshi; Inoue, Osamu

    2009-01-01

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [ 14 C]2-deoxyglucose ([ 14 C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [ 14 C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [ 14 C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [ 14 C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  18. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  19. CNF1 Enhances Brain Energy Content and Counteracts Spontaneous Epileptiform Phenomena in Aged DBA/2J Mice.

    Directory of Open Access Journals (Sweden)

    Sara Travaglione

    Full Text Available Epilepsy, one of the most common conditions affecting the brain, is characterized by neuroplasticity and brain cell energy defects. In this work, we demonstrate the ability of the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1 to counteract epileptiform phenomena in inbred DBA/2J mice, an animal model displaying genetic background with an high susceptibility to induced- and spontaneous seizures. Via modulation of the Rho GTPases, CNF1 regulates actin dynamics with a consequent increase in spine density and length in pyramidal neurons of rat visual cortex, and influences the mitochondrial homeostasis with remarkable changes in the mitochondrial network architecture. In addition, CNF1 improves cognitive performances and increases ATP brain content in mouse models of Rett syndrome and Alzheimer's disease. The results herein reported show that a single dose of CNF1 induces a remarkable amelioration of the seizure phenotype, with a significant augmentation in neuroplasticity markers and in cortex mitochondrial ATP content. This latter effect is accompanied by a decrease in the expression of mitochondrial fission proteins, suggesting a role of mitochondrial dynamics in the CNF1-induced beneficial effects on this epileptiform phenotype. Our results strongly support the crucial role of brain energy homeostasis in the pathogenesis of certain neurological diseases, and suggest that CNF1 could represent a putative new therapeutic tool for epilepsy.

  20. Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

    Science.gov (United States)

    Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

    2017-11-04

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Analysis of local perfusion rate (LPR) and local glucose transport rate (LGTR) in brain and heart in man by means of C-11-methyl-D-glucose (CMG) and dynamic positron emission tomography (dPET)

    International Nuclear Information System (INIS)

    Vyska, K.; Freundlieb, C.; Hoeck, A.; Becker, V.; Schmidt, A.; Feinendegen, L.E.; Kloster, G.; Stoecklin, G.; Heiss, W.D.

    1982-01-01

    A method has been developed to measure simultaneously the LPR and LGTR. CMG is used as an indicator. The transaxial distribution of activity in organism is registered with dPET. On the basis of a mathematical model, the LPR and LGTR can be calculated in terms of parameters of the time activity curves registered over different brain or heart regions and over the sup. long. sinus (brain) or the ventricular cavity (heart) (blood activity). The method was used in 10 normal subjects and 20 patients with ischemic brain or heart disease. The values of LGTR range from 0.43 to 0.6 μmol/min g in normal cortex and from 0.09 to 0.12 μmol/min g in normal white matter. The LPR was 0.9-098 ml/min g for the cortex and 0.3-0.4 ml/min g for the white matter. In patients with stroke the ischemic defects appeared to be larger in CMG scans than in CT. The results obtained in a patient with left homonymous hemianopia, caused by infarctions in the distribution area of RMCA, and in a patient with TIA, demonstrate that the inactivation of morphologically intact, cerebral cortex, observed in stroke patients, may be caused by undercutting of cortical fiber tracts as well as by the impairment of the glucose transport systems in the inactivated area. In myocardial studies the LPR in normal left myocardium was 0.68 ml/min g (subendocardium 0.74 ml/min g; subepicardiuim 0.65 ml/min g). In patients with old myocardial infarction, the infarcted areas could be easily recognized as accumulation defects. The results obtained in a patient with narrowing of the RCA indicate that repeated exposure of myocardial tissue to transient ischemia produces an irreversible damage of the glucose transport system. We conclude from the data that for diagnostic evaluation of ultimate brain or heart damage simultaneous quantitative assessment of both LPR and LGTR is of basic importance. (Author)

  2. Contents

    Directory of Open Access Journals (Sweden)

    Editor IJRED

    2012-11-01

    Full Text Available International Journal of Renewable Energy Development www.ijred.com Volume 1             Number 3            October 2012                ISSN 2252- 4940   CONTENTS OF ARTICLES page Design and Economic Analysis of a Photovoltaic System: A Case Study 65-73 C.O.C. Oko , E.O. Diemuodeke, N.F. Omunakwe, and E. Nnamdi     Development of Formaldehyde Adsorption using Modified Activated Carbon – A Review 75-80 W.D.P Rengga , M. Sudibandriyo and M. Nasikin     Process Optimization for Ethyl Ester Production in Fixed Bed Reactor Using Calcium Oxide Impregnated Palm Shell Activated Carbon (CaO/PSAC 81-86 A. Buasri , B. Ksapabutr, M. Panapoy and N. Chaiyut     Wind Resource Assessment in Abadan Airport in Iran 87-97 Mojtaba Nedaei       The Energy Processing by Power Electronics and its Impact on Power Quality 99-105 J. E. Rocha and B. W. D. C. Sanchez       First Aspect of Conventional Power System Assessment for High Wind Power Plants Penetration 107-113 A. Merzic , M. Music, and M. Rascic   Experimental Study on the Production of Karanja Oil Methyl Ester and Its Effect on Diesel Engine 115-122 N. Shrivastava,  , S.N. Varma and M. Pandey  

  3. Evidence that metyrapone can act as a stressor: effect on pituitary-adrenal hormones, plasma glucose and brain c-fos induction.

    Science.gov (United States)

    Rotllant, David; Ons, Sheila; Carrasco, Javier; Armario, Antonio

    2002-08-01

    Metyrapone, a 11-beta steroid hydroxylase inhibitor that blocks stress-induced glucocorticoid release, is extensively used to study the physiological and behavioural roles of glucocorticoids. However, there is circumstantial evidence suggesting that metyrapone could act as a pharmacological stressor. Thus, the effects of various doses of metyrapone on two well-characterized stress markers (ACTH and glucose) were studied in male rats. Metyrapone administration, while exerting a modest effect on plasma corticosterone levels, dose-dependently increased plasma ACTH and glucose levels. Using the highest doses previously tested (200 mg/kg) we further observed, as evaluated by fos-like immunoreactivity (FLI), a strong activation of a wide range of brain areas, including the parvocellular region of the hypothalamic paraventricular nucleus (PVNp), the origin of the main ACTH secretagogues. Metyrapone-induced FLI was observed in neocortical and allocortical areas, in several limbic, thalamic and hypothalamic nuclei and, to a lesser extent, in the brainstem. In a final experiment, a dose-response study of metyrapone-induced FLI was carried out focusing on selected brain areas. The study revealed that the paraventricular thalamic nucleus and central amygdala were the areas most sensitive to metyrapone as they responded even to the lowest dose of the drug. Most areas, among them the PVNp, only showed enhanced FLI with the two highest doses, i.e. when it was associated with ACTH and glucose responses. These data suggest that some of the effects of metyrapone could be due to its stressful properties rather than its ability to inhibit glucocorticoid synthesis. The exact mechanisms involved remain to be established.

  4. Hierarchical clustering of Alzheimer and "normal" brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    NARCIS (Netherlands)

    Cutts, DA; Spyrou, NM; Maguire, RP; Leenders, KL

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element

  5. Modeling the ischemic blood-brain barrier; the effects of oxygen-glucose deprivation (OGD) on endothelial cells in culture

    DEFF Research Database (Denmark)

    Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

    Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... pathways across the barrier in ischemic and postischemic brain endothelium is important for developing new medical therapies capable to exploit the barrier changes occurring during/after ischemia to permeate in the brain and treat this devastating disease. Materials and Methods - Primary cultures...... the wall of brain capillaries. The restrictive nature of the BBB is due to the tight junctions (TJs), which seal the intercellular clefts, limiting the paracellular diffusion, efflux transporters, which extrude xenobiotics, and metabolizing enzymes, which may break down or convert molecules during...

  6. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Directory of Open Access Journals (Sweden)

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  7. The protective role of isorhamnetin on human brain microvascular endothelial cells from cytotoxicity induced by methylglyoxal and oxygen-glucose deprivation.

    Science.gov (United States)

    Li, Wenlu; Chen, Zhigang; Yan, Min; He, Ping; Chen, Zhong; Dai, Haibin

    2016-02-01

    As the first target of stroke, cerebral endothelial cells play a key role in brain vascular repair and maintenance, and their function is impeded in diabetes. Methylglyoxal (MGO), a reactive dicarbonyl produced during glucose metabolism, accumulates in diabetic patients. MGO and MGO-induced advanced glycation end-products (AGEs) could ameliorate stroke-induced brain vascular damage, closely related with ECs dysfunction. Using MGO plus oxygen-glucose deprivation (OGD) to mimic diabetic stroke, we reported the protective effect of isorhamnetin on OGD-induced cytotoxicity after MGO treatment on primary human brain microvascular endothelial cells (HBMEC) and explored the underlying mechanisms. Treatment of MGO for 24 h significantly enhanced 3-h OGD-induced HBMEC toxic effect, which was inhibited by pretreatment of isorhamnetin (100 μmol/L). Moreover, the protective effect of isorhamnetin is multiple function dependent, which includes anti-inflammation, anti-oxidative stress and anti-apoptosis effects. Besides its well-known inhibition on the mitochondria-dependent or intrinsic apoptotic pathway, isorhamnetin also reduced activation of the extrinsic apoptotic pathway, as characterized by the decreased expression and activity of caspase 3 and caspase 8. Furthermore, pretreatment with isorhamnetin specifically inhibited FAS/FASL expression and suppressed nuclear factor-kappa B nuclear translocation. Taken together, our results indicated that isorhamnetin protected against OGD-induced cytotoxicity after MGO treatment in cultured HBMEC due to its multiple protective effects and could inhibit Fas-mediated extrinsic apoptosis. Therefore, isorhamnetin is a promising reagent for the treatment of hyperglycemia and ischemia-induced cerebral vascular degeneration. A proposed model of the potential protective mechanism of isorhamnetin, a metabolite of quercetin, on methylglyoxal (MGO) treatment plus oxygen-glucose deprivation (OGD) exposure-induced cytotoxicity in cultured human

  8. MR-visible water content in human brain: a proton MRS study

    DEFF Research Database (Denmark)

    Christiansen, P; Toft, P B; Gideon, P

    1994-01-01

    . The major drawbacks are the necessity to make the assumptions that the water concentrations in the brain and that all tissue water is MR-visible. A number of in vivo measurements were carried out to estimate the concentration of MR-visible water in the brain of healthy volunteers divided into four age...... and biochemical data published, suggest that only a small fraction (invisible.(ABSTRACT TRUNCATED AT 250 WORDS)...

  9. Influence of age and splanchnic nerve on the action of melatonin in the adrenomedullary catecholamine content and blood glucose level in the avian group.

    Science.gov (United States)

    Mahata, S K; Mandal, A; Ghosh, A

    1988-01-01

    A single intraperitoneal (IP) melatonin injection (0.5 mg/100 g body wt.) caused an increase in norepinephrine (NE) fluorescence and elevation of NE content in newly-hatched pigeons (Columba livia), but a reduction of NE fluorescence and depletion of NE content in the adrenal medulla of newly-hatched crows (Corvus splendens) after 0.5 h of treatment. In contrast, in adults melatonin caused increase in NE fluorescence and elevation of NE content only in the parakeet (Psittacula krameri). Half an hour of IP melatonin treatment (0.5 mg/100 g body wt.) induced release of epinephrine (E) from the adrenal medulla of newly-hatched pigeon and parakeet. In contrast, in the adults melatonin caused more than a two-fold increase in E in the pigeon, and a significant increase in the crow. Single IP melatonin injection (0.5 mg/100 g body wt.) caused hypoglycemia in the newly-hatched parakeet and adult pigeon, and hyperglycemia in newly-hatched pigeon after 0.5 h of treatment. Melatonin failed to regulate glucose homoeostasis in newly-hatched and adult crow. Splanchnic denervation of the left adrenal gland was performed in the adult pigeon. The right adrenal served as the innervated gland. Melatonin-induced modulation of catecholamines following a single IP injection (0.5 mg/100 g body wt.) revealed significant increases in NE fluorescence and NE content at 4 and 12 h after treatment in the denervated gland only, which gradually approached normal levels 9 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  11. Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

    Science.gov (United States)

    Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

    2017-02-15

    Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

  12. Comparative effect of thymol or its glucose conjugate, thymol-β-D-glucopyranoside, on Campylobacter in avian gut contents.

    Science.gov (United States)

    Epps, Sharon V R; Harvey, Roger B; Byrd, J Allen; Petrujkić, Branko T; Sedej, Ivana; Beier, Ross C; Phillips, Timothy D; Hume, Michael E; Anderson, Robin C; Nisbet, David J

    2015-01-01

    Campylobacter jejuni is an important human food-borne pathogen that can contaminate meat and poultry during processing. Consequently, strategies are sought to reduce the carriage of C. jejuni in food animals before they arrive at the abattoir. Thymol is a natural product that reduces survivability of Campylobacter in vitro, but its rapid absorption from the proximal alimentary tract limits its bactericidal efficacy in vivo. Thymol-β-D-glucopyranoside is more resistant to absorption than free thymol, but its administration to chickens has not been reported. In the present studies, 1 mM thymol-β-D-glucopyranoside was shown to exhibit near equal anti-Campylobacter activity as 1 mM thymol when incubated anaerobically in avian crop or cecal contents in vitro, resulting in reductions of 1.10-2.32 log10 colony forming units mL(-1) in C. jejuni concentrations after 24 h incubation. In a follow-up live animal study, oral administration of thymol-β-D-glucopyranoside, but not free thymol, significantly lowered (>10-fold) recovery of Campylobacter from the crop of market-aged broilers when compared to placebo-treated controls (n = 6 broilers/treatment). Neither thymol-β-D-glucopyranoside nor thymol affected recovery of Campylobacter from cecal contents of the treated broilers. These results indicate that rapid absorption or passage of free thymol from the crop precluded its anti-Campylobacter activity at this site and throughout the entire gastrointestinal tract. Conversely, lower recovery of Campylobacter from the crop of birds treated with thymol-β-D-glucopyranoside indicates this conjugate was retained and able to be hydrolyzed to biologically active free thymol at this site as intended, yet was not sufficiently protected to allow passage of efficacious amounts of the intact glycoside to the lower gut. Nevertheless, these results warrant further research to see if higher doses or encapsulation of thymol-β-D-glucopyranoside or similar glycosides may yield an

  13. Rapid whole brain myelin water content mapping without an external water standard at 1.5T.

    Science.gov (United States)

    Nguyen, Thanh D; Spincemaille, Pascal; Gauthier, Susan A; Wang, Yi

    2017-06-01

    The objective of this study is to develop rapid whole brain mapping of myelin water content (MWC) at 1.5T. The Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) pulse sequence originally developed for myelin water fraction (MWF) mapping was modified to obtain fast mapping of T1 and receiver coil sensitivity needed for MWC computation. The accuracy of the proposed T1 mapping was evaluated by comparing with the standard IR-FSE method. Numerical simulations were performed to assess the accuracy and reliability of the proposed MWC mapping. We also compared MWC values obtained with either cerebrospinal fluid (CSF) or an external water tube attached to the subject's head as the water reference. Our results from healthy volunteers show that whole brain MWC mapping is feasible in 7min and provides accurate brain T1 values. Regional brain WC and MWC measurements obtained with the internal CSF-based water standard showed excellent correlation (R>0.99) and negligible bias within narrow limits of agreement compared to those obtained with an external water standard. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Decreased weight, DNA, RNA and protein content of the brain after neutron irradiation of the 18-day mouse embryo

    International Nuclear Information System (INIS)

    Antal, S.; Fonagy, A.; Hidvegi, E.J.; Fueloep, Z.; Vogel, H.H. Jr.

    1984-01-01

    Pregnant mice were irradiated with 0.5 Gy fission neutrons on the eighteenth day of gestation. Average litter size at birth was unchanged but mortality increased 5-6 fold in the first 3 days. Irradiated mice were the same weight as control mice at birth but showed a progressively increasing weight deficiency up to at least 36 days compared to controls. Brain weight was 37, 45 and 25% less in 2-, 3- and 52-week old irradiated animals; the ratio of brain weight to body weight was 25, 27 and 13% less. The concentrations of DNA, RNA and protein (mg/g wet tissue) were the same in irradiated and control mice in brain and liver at all three ages. Total DNA, RNA and protein contents of whole brain after irradiation were 56-75% of control levels. No definite decrease was observed in liver. Histological study at 6 hours after irradiation showed nuclear pyknosis in the central nervous system from definite to very severe according to the part examined. It is concluded that damage to the central nervous system of the 18-day mouse foetus is mainly due to killing and/or inhibition of the differentiation of neuroblasts. (author)

  15. Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging.

    Science.gov (United States)

    Bernier, Michaël; Croteau, Etienne; Castellano, Christian-Alexandre; Cunnane, Stephen C; Whittingstall, Kevin

    2017-04-15

    Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

    Science.gov (United States)

    Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

    2013-01-01

    To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

  17. Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

    Science.gov (United States)

    Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

    2013-01-01

    Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease

  18. DNA content of rodent brains during maturation and aging, and autoradiography of postnatal DNA synthesis in monkey brain

    International Nuclear Information System (INIS)

    Howard, E.

    1973-01-01

    [ 3 H]Thymidine is taken up by cells synthesizing DNA prepatory to cell division and remains incorporated in the DNA molecules as a lasting radioactive cell marker unless diluted out by repeated cell divisions. With the mouse and rat, histological studies after [ 3 H]thymidine injections have demonstrated that the cells of the external granular layer of the cerebellum proliferate abundantly during the first 2 weeks of postnatal life. Development of the primate brain is a gradual process extending over a much longer time than is required in the rodent. Despite the relative histological maturity of the monkey cerebellum at birth, the cells of the external granular layer are still actively synthesizing DNA at this time. Two monkeys were given [ 3 H]thymidine at birth and killed within 4 hours. Intense radioactivity was present in the cells of the external granular layer. Cells near the Prukinje perikarya were rather frequently labelled in this monkey, as described by Miale and Sidman in the mouse. In the molecular layer and in the body of the granular layer, relatively few cells were labelled. The labelling was present throughout the cerebellum, although the number of cells labelled varied from one microscopic field to another

  19. Content-based image retrieval using spatial layout information in brain tumor T1-weighted contrast-enhanced MR images.

    Science.gov (United States)

    Huang, Meiyan; Yang, Wei; Wu, Yao; Jiang, Jun; Gao, Yang; Chen, Yang; Feng, Qianjin; Chen, Wufan; Lu, Zhentai

    2014-01-01

    This study aims to develop content-based image retrieval (CBIR) system for the retrieval of T1-weighted contrast-enhanced MR (CE-MR) images of brain tumors. When a tumor region is fed to the CBIR system as a query, the system attempts to retrieve tumors of the same pathological category. The bag-of-visual-words (BoVW) model with partition learning is incorporated into the system to extract informative features for representing the image contents. Furthermore, a distance metric learning algorithm called the Rank Error-based Metric Learning (REML) is proposed to reduce the semantic gap between low-level visual features and high-level semantic concepts. The effectiveness of the proposed method is evaluated on a brain T1-weighted CE-MR dataset with three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor). Using the BoVW model with partition learning, the mean average precision (mAP) of retrieval increases beyond 4.6% with the learned distance metrics compared with the spatial pyramid BoVW method. The distance metric learned by REML significantly outperforms three other existing distance metric learning methods in terms of mAP. The mAP of the CBIR system is as high as 91.8% using the proposed method, and the precision can reach 93.1% when the top 10 images are returned by the system. These preliminary results demonstrate that the proposed method is effective and feasible for the retrieval of brain tumors in T1-weighted CE-MR Images.

  20. Content-based image retrieval using spatial layout information in brain tumor T1-weighted contrast-enhanced MR images.

    Directory of Open Access Journals (Sweden)

    Meiyan Huang

    Full Text Available This study aims to develop content-based image retrieval (CBIR system for the retrieval of T1-weighted contrast-enhanced MR (CE-MR images of brain tumors. When a tumor region is fed to the CBIR system as a query, the system attempts to retrieve tumors of the same pathological category. The bag-of-visual-words (BoVW model with partition learning is incorporated into the system to extract informative features for representing the image contents. Furthermore, a distance metric learning algorithm called the Rank Error-based Metric Learning (REML is proposed to reduce the semantic gap between low-level visual features and high-level semantic concepts. The effectiveness of the proposed method is evaluated on a brain T1-weighted CE-MR dataset with three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor. Using the BoVW model with partition learning, the mean average precision (mAP of retrieval increases beyond 4.6% with the learned distance metrics compared with the spatial pyramid BoVW method. The distance metric learned by REML significantly outperforms three other existing distance metric learning methods in terms of mAP. The mAP of the CBIR system is as high as 91.8% using the proposed method, and the precision can reach 93.1% when the top 10 images are returned by the system. These preliminary results demonstrate that the proposed method is effective and feasible for the retrieval of brain tumors in T1-weighted CE-MR Images.

  1. Dynamics of trimming the content of face representations for categorization in the brain.

    Directory of Open Access Journals (Sweden)

    Nicola J van Rijsbergen

    2009-11-01

    Full Text Available To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1 over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2 concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g., the eyes to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g., the wide opened eyes in 'fear'; the detailed mouth in 'happy'. Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300.

  2. Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

    Directory of Open Access Journals (Sweden)

    Xue-Yuan Li

    2016-10-01

    Full Text Available Alzheimer’s disease (AD is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1 transgenic (Tg mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr. Morris water maze (MWM was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD. By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD. Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

  3. Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

    Science.gov (United States)

    Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

    2016-10-18

    Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

  4. The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice

    Directory of Open Access Journals (Sweden)

    Lumei Liu

    2016-07-01

    Full Text Available Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n=5 with varying fat (control/high and iron (control/high/low contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin-H (FtH protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P<0.05. The high-fat diet altered brain iron contents and ferritin-H (FtH protein and mRNA expressions in a regional-specific manner: 1 high-fat diet significantly decreased the brain iron content in the striatum (P<0.05, but not other regions; and 2 thalamus has a more distinct change in FtH mRNA expression compared to other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P<0.05. Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings will lay

  5. Immature rat brain slices exposed to oxygen-glucose deprivation as an in vitro model of neonatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Fernández-López, David; Martínez-Orgado, José; Casanova, Ignacio; Bonet, Bartolomé; Leza, Juan Carlos; Lorenzo, Pedro; Moro, Maria Angeles; Lizasoain, Ignacio

    2005-06-30

    To analyze whether exposure to oxygen-glucose deprivation (OGD) of immature rat brain slices might reproduce the main pathophysiologic events leading to neuronal death in neonatal hypoxic-ischemic encephalopathy (NHIE), 500 microm-thick brain slices were obtained from 7-day-old Wistar rats, and incubated in oxygenated physiological solution. In OGD group, oxygen and glucose were removed from the medium for 10-30 min (n = 25); then, slices were re-incubated in normal medium. In control group the medium composition remained unchanged (CG, n = 30). Medium samples were obtained every 30 min for 3 h. To analyze neuronal damage, slices were stained with Nissl and CA1 area of hippocampus and cortex were observed under microscopy. In addition, neuronal death was quantified as LDH released to the medium determined by spectrophotometry. Additionally, medium glutamate (Glu) levels were determined by HPLC and those of TNFalpha by ELISA, whereas inducible nitric oxide synthase expression was determined by Western blot performed on slices homogenate. Optimal OGD time was established in 20 min. After OGD, a significant decrease in the number of neurones in hippocampus and cortex was observed. LDH release was maximal at 30 min, when it was five-fold greater than in CG. Furthermore, medium Glu concentrations were 200 times greater than CG levels at the end of OGD period. A linear relationship between Glu and LDH release was demonstrated. Finally, 3 h after OGD a significant induction of iNOS as well as an increase in TNFalpha release were observed. In conclusion, OGD appears as a feasible and reproducible in vitro model, leading to a neuronal damage, which is physiopathologically similar to that found in NHIE.

  6. Toxic effect of lithium in mouse brain

    International Nuclear Information System (INIS)

    Dixit, P.K.; Smithberg, M.

    1988-01-01

    The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into 14 CO 2 /mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed

  7. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

    Science.gov (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

    2017-11-04

    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Calcitonin gene-related peptide: neuroendocrine communication between the pancreas, gut, and brain in regulation of blood glucose.

    Science.gov (United States)

    Pendharkar, Sayali A; Walia, Monika; Drury, Marie; Petrov, Maxim S

    2017-11-01

    Calcitonin gene-related peptide (CGRP), a ubiquitous neuropeptide, plays a diverse and intricate role in chronic low-grade inflammation, including conditions such as obesity, type 2 diabetes, and diabetes of the exocrine pancreas. Diabetes of exocrine pancreas is characterised by chronic hyperglycemia and is associated with persistent low-grade inflammation and altered secretion of certain pancreatic and gut hormones. While CGRP may regulate glucose homeostasis and the secretion of pancreatic and gut hormones, its role in chronic hyperglycemia after acute pancreatitis (CHAP) is not known. The aim of this study was to investigate the association between CGRP and CHAP. Fasting blood samples were collected to measure insulin, HbA1c, CGRP, amylin, C-peptide, glucagon, pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide, glicentin, glucagon-like peptide-1 and 2, and oxyntomodulin. Modified Poisson regression analysis and linear regression analyses were conducted. Five statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 patients were recruited. CGRP was significantly associated with CHAP in all five models (P-trend <0.005). Further, it was significantly associated with oxyntomodulin (P<0.005) and glucagon (P<0.030). Oxyntomodulin and glucagon independently contributed 9.7% and 7%, respectively, to circulating CGRP variance. Other pancreatic and gut hormones were not significantly associated with CGRP. CGRP is involved in regulation of blood glucose in individuals after acute pancreatitis. This may have translational implications in prevention and treatment of diabetes of the exocrine pancreas.

  9. Comparing amyloid-β deposition, neuroinflammation, glucose metabolism, and mitochondrial complex I activity in brain: a PET study in aged monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Tsukada, Hideo; Nishiyama, Shingo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro [Hamamatsu Photonics K.K., Central Research Laboratory, Shizuoka (Japan)

    2014-11-15

    The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys. PET scans with {sup 11}C-PIB (Aβ), {sup 18}F-BCPP-EF (MC-I), {sup 11}C-DPA-713 (TSPO), and {sup 18}F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. {sup 11}C-PIB binding to Aβ and {sup 11}C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V{sub T}) of {sup 18}F-BCPP-EF and rCMRglc with {sup 18}F-FDG were calculated using arterial blood sampling. Isoflurane did not affect MC-I activity measured in terms of {sup 18}F-BCPP-EF uptake in living brain. There was a significant negative correlation between {sup 18}F-BCPP-EF binding (V{sub T}) and {sup 11}C-PIB uptake (SUVR), and there was a significant positive correlation between {sup 11}C-DPA-713 uptake (SUV) and {sup 11}C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and {sup 11}C-PIB uptake. {sup 18}F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain. (orig.)

  10. Is cerebral glucose metabolism related to blood-brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?: A 18F-FDG PET/CT study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Ursini, Francesco; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Toniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

    2016-09-01

    The aim of this study was to investigate the relationships between blood-brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(F) fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects.

  11. Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

    Science.gov (United States)

    Jeong, H S; Park, J S; Song, I U; Chung, Y A; Rhie, S J

    2017-01-01

    Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02). Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Tsui, Wai H.; De Leon, Mony J. [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Wang, Gene-Jack; Fowler, Joanna [Brookhaven National Laboratory, Upton, NY (United States); Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy)

    2007-09-15

    To examine CMRglc measures and corresponding glucose transport (K{sub 1} and k{sub 2}) and phosphorylation (k{sub 3}) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 {+-} 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 {+-} 9 years, three females, median MMSE 30). Absolute CMRglc ({mu}mol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k{sub 3} reductions were found in the hippocampus, PCC and amygdala. K{sub 1} reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

  13. The effect of emotional content on brain activation and the late positive potential in a word n-back task.

    Directory of Open Access Journals (Sweden)

    Juliane Kopf

    Full Text Available INTRODUCTION: There is mounting evidence for the influence of emotional content on working memory performance. This is particularly important in light of the emotion processing that needs to take place when emotional content interferes with executive functions. In this study, we used emotional words of different valence but with similar arousal levels in an n-back task. METHODS: We examined the effects on activation in the prefrontal cortex by means of functional near-infrared spectroscopy (fNIRS and on the late positive potential (LPP. FNIRS and LPP data were examined in 30 healthy subjects. RESULTS: BEHAVIORAL RESULTS SHOW AN INFLUENCE OF VALENCE ON THE ERROR RATE DEPENDING ON THE DIFFICULTY OF THE TASK: more errors were made when the valence was negative and the task difficult. Brain activation was dependent both on the difficulty of the task and on the valence: negative valence of a word diminished the increase in activation, whereas positive valence did not influence the increase in activation, while difficulty levels increased. The LPP also differentiated between the different valences, and in addition was influenced by the task difficulty, the more difficult the task, the less differentiation could be observed. CONCLUSIONS: Summarized, this study shows the influence of valence on a verbal working memory task. When a word contained a negative valence, the emotional content seemed to take precedence in contrast to words containing a positive valence. Working memory and emotion processing sites seemed to overlap and compete for resources even when words are carriers of the emotional content.

  14. Content of NCAM in the brain and pancreas of rats in response to endointoxication under conditions of experimental chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    V. A. Makarchuk

    2014-08-01

    Full Text Available The study was undertaken to examine the influence of chronic pancreatitis on the distribution of neuronal cell adhesion molecule (NCAM in the pancreas and various brain regions of rats under the conditions of endogenous intoxication. The study was conducted using 36 white nonlinear male rats (6 months old, 190–220 g. To develop the state of chronic pancreatitis, animals were subjected tolaparotomy under general anesthesia and prolonged occlusion of the pancreatic duct. The morphological examination of pancreatic tissue hasbeen performed to confirm the chronic pancreatitis development in animals. Biochemical evaluation of the pancreatic fibrosis has been performed by measuring plasma levels of hyaluronic acid, hydroxyproline and protein-free hydroxyproline. The intensity of free radical oxidation has been assessed by the change in the concentration of TBA-active products in plasma. The level of endotoxemia has been determinedby the content of average weight molecules in plasma. Protein fractions were extracted from the pancreas and various parts of the rat brain and the levels of soluble (sNCAM and membrane (mNCAM proteins were studied with the use of the competitive ELISA. Total protein in the obtained fractions was measured by the Bradford assay. Occlusion of the pancreatic duct resultedin significant atrophy of acinar tissue, fibrosis and disfunction of the pancreas along with the decreasing in the antioxidant defense of animals. The present study shows developing of endointoxication in experimentalrats, signified by considerable increase of molecules with average weight in plasma due to the activation of lipid peroxidation. It was established that, as a result of the experimental pancreas dysfunction, significant redistribution of soluble and membrane forms of NCAM took place, more especially in the cerebellum and thalamus of rats; it caused changing of cell-cell adhesion in these brain regions. Multidirectional NCAM distribution in the

  15. Multimedia human brain database system for surgical candidacy determination in temporal lobe epilepsy with content-based image retrieval

    Science.gov (United States)

    Siadat, Mohammad-Reza; Soltanian-Zadeh, Hamid; Fotouhi, Farshad A.; Elisevich, Kost

    2003-01-01

    This paper presents the development of a human brain multimedia database for surgical candidacy determination in temporal lobe epilepsy. The focus of the paper is on content-based image management, navigation and retrieval. Several medical image-processing methods including our newly developed segmentation method are utilized for information extraction/correlation and indexing. The input data includes T1-, T2-Weighted MRI and FLAIR MRI and ictal and interictal SPECT modalities with associated clinical data and EEG data analysis. The database can answer queries regarding issues such as the correlation between the attribute X of the entity Y and the outcome of a temporal lobe epilepsy surgery. The entity Y can be a brain anatomical structure such as the hippocampus. The attribute X can be either a functionality feature of the anatomical structure Y, calculated with SPECT modalities, such as signal average, or a volumetric/morphological feature of the entity Y such as volume or average curvature. The outcome of the surgery can be any surgery assessment such as memory quotient. A determination is made regarding surgical candidacy by analysis of both textual and image data. The current database system suggests a surgical determination for the cases with relatively small hippocampus and high signal intensity average on FLAIR images within the hippocampus. This indication pretty much fits with the surgeons" expectations/observations. Moreover, as the database gets more populated with patient profiles and individual surgical outcomes, using data mining methods one may discover partially invisible correlations between the contents of different modalities of data and the outcome of the surgery.

  16. β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

    Directory of Open Access Journals (Sweden)

    Cilio Corrado

    2010-12-01

    Full Text Available Abstract Background Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-α through TNF receptor (TNFR 1. Adrenoceptor (AR activation is known to modulate the immune response and synaptic transmission. The possible protective effect of α˜ and β˜AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS and subsequently subjected to oxygen-glucose deprivation (OGD. Method Hippocampal slices from mice were obtained at P6, and were grown in vitro for 9 days on nitrocellulose membranes. Slices were treated with β1(dobutamine-, β2(terbutaline-, α1(phenylephrine- and α2(clonidine-AR agonists (5 and 50 μM, respectively during LPS (1 μg/mL, 24 h -exposure followed by exposure to OGD (15 min in a hypoxic chamber. Cell death in the slice CA1 region was assessed by propidium iodide staining of dead cells. Results Exposure to LPS + OGD caused extensive cell death from 4 up to 48 h after reoxygenation. Co-incubation with β1-agonist (50 μM during LPS exposure before OGD conferred complete protection from cell death (P -/- and TNFR2-/- slices exposed to LPS followed by OGD. Conclusions Our data demonstrate that activation of both β1- and β2-receptors is neuroprotective and may offer mechanistic insights valuable for development of neuro-protective strategies in neonates.

  17. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

    Science.gov (United States)

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

    2017-05-01

    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  18. Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke.

    Science.gov (United States)

    Tan, Sha; Shan, Yilong; Wang, Yuge; Lin, Yinyao; Liao, Siyuan; Deng, Zhezhi; Zhou, Li; Cai, Wei; Zeng, Qin; Zhang, Lei; Zhang, Bingjun; Men, Xuejiao; Li, Haiyan; Hu, Xueqiang; Wu, Changyou; Peng, Lisheng; Lu, Zhengqi

    2017-07-01

    Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. Correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Bing-Feng Tian

    2018-07-01

    Full Text Available Objective: To study the correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury. Methods: A total of 110 patients with traumatic brain injury who were treated in our hospital between January 2015 and December 2016 were collected as the observation group, and 60 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. Serum GFAP, S100B and NSE levels as well as oxidative stress index and insulin resistance index levels of two groups of subjects were detected, and Pearson test was used to further evaluate the correlation of serum GFAP, S100B and NSE contents with oxidative stress response and insulin resistance in patients with traumatic brain injury. Results: Serum GFAP, S100B and NSE contents of observation group were significantly higher than those of normal control group; serum oxidative stress indexes MDA, MPO and LPO contents were higher than those of normal control group while SOD and TAC contents were lower than those of normal control group; serum insulin resistance indexes GLU, INS and HOMA-IR levels were higher than those of control group. Pearson test showed that serum GFAP, S100B and NSE contents in patients with traumatic brain injury were directly correlated with post-traumatic oxidative stress and insulin resistance. Conclusion: The serum GFAP, S100B and NSE contents increase in patients with traumatic brain injury, and the increase is directly correlated with the oxidative stress and insulin resistance.

  20. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  1. Variações do conteúdo de glucose, frutose e sorbitol em gemas e ramos de macieira durante a dormência Variations of glucose, frutose and sorbitol content in buds and stems of apple tree during the dormancy period

    Directory of Open Access Journals (Sweden)

    Ruy Inacio Neiva de Carvalho

    2006-12-01

    Full Text Available O objetivo deste trabalho foi determinar as variações do conteúdo de glucose, frutose e sorbitol em gemas e ramos de um ano de macieira durante o período de dormência. Os ramos da cultivar "Imperial Gala" foram coletados em Porto Amazonas-PR, em intervalos de 21 dias, de abril a agosto (19/04, 10/05, 31/05, 21/06, 12/07, 02/08 e 23/08, e receberam ou não tratamento com frio suplementar de 1.440 horas à temperatura de 4 a 7°C. As análises dos carboidratos foram realizadas em gemas e porções de ramos adjacentes às primeiras por cromatografia líquida de alta eficiência (HPLC. Ocorreu um acúmulo de glucose, frutose e sorbitol nas gemas de macieira durante a dormência. O acúmulo de glucose e frutose nos ramos aconteceu até o início de agosto quando, em seguida, houve redução, enquanto o sorbitol decresceu até junho e, em seguida, elevou-se até o final de agosto. O tratamento com frio ao longo da dormência modificou as variações dos conteúdos de carboidratos nas gemas e ramos de macieira.This research was aimed at evaluating the variations of glucose, frutose and sorbitol content in one year old buds and stems of apple trees during the dormancy period. The stems of cv. Imperial Gala were collected in Porto Amazonas, Parana State, Brazil, at intervals of 21 days from April to August (April 19th, May 10th, May 31st, June 21st, July 12th, August 2nd and August 23rd and were treated or not with 1,440 hours of chill (4 to 7°C. The carbohydrates were analysed in buds and stem tissues close to buds by high performance liquid chromatography (HPLC. There was an increase of glucose, frutose and sorbitol content in apple tree buds during the dormancy. An increase of glucose and frutose content in stems occured until August 2nd followed by a significative reduction, while the sorbitol content decreased until June 21st followed by an increase until August 31st. The chill treatment during the dormancy period modified the variations of

  2. 14C-dopamine microinjected into the brain-stem of the rat: dispersion kinetics, site content and functional dose

    International Nuclear Information System (INIS)

    Myers, R.D.; Hoch, D.B.

    1978-01-01

    A morphological analysis was undertaken of both the dispersion characteristics and tissue content of dopamine (DA) microinjected acutely into the brain-stem of the anesthetized rat. 14C-DA, with a specific activity of 56-62 mCi/mMol, was infused unilaterally into the pars compacta of the substantia nigra in one of four test volumes: 0.5, 1.0, 4.0 or 8.0 microliters. The concentration of the 14C-DA solution was 1.0 microCi/microliter, equivalent to 3.01 micrograms/microliters, which was delivered at an injection rate of 1.0 microliter per 45 sec. At an interval of either one min or 15 min following the microinjection, the rat's brain was removed rapidly from its calvarium, flash frozen and then cut in the coronal plane on a freezing microtome in 500 micron slabs. After each of the respective serial slabs was mounted on glass, the Eik Nes-Brizzee trochar technique for the discrete removal of tissue samples was used to obtain 0.5 mm dia. cylindrical plugs of meso-diencephalic tissue at distances from the site of injection ranging from 0.5 to 2.5 mm, center to center. Each sample plug was subsequently solubilized and 14C-DA activity quantitated by liquid scintillation spectrometry. The results show that regardless of volume, the spatial patterning of the microinjected solution assumes a tear-drop or pear shape, not a sphere. Further, as the volume of the injection is increased from 0.5 to 8.0 microliters, the magnitude of the dispersion of 14C-DA is enhanced throughout the surrounding parenchyma, but not in a linear fashion

  3. The effects of incretin hormones on cerebral glucose metabolism in health and disease

    DEFF Research Database (Denmark)

    Nilsson, Malin; Gjedde, Albert; Brock, Birgitte

    2017-01-01

    Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies......, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia. GLP-1, when administered as long-acting analogues...... or intravenously, appears to decrease transport of glucose in normoglycaemic conditions, without affecting the total cerebral glucose content. During hypoglycaemia this effect seems abated, whereas during hyperglycaemia GLP-1 regulates cerebral glucose metabolism towards stable levels resembling normoglycaemia...

  4. GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion

    DEFF Research Database (Denmark)

    Cani, Patrice D; Holst, Jens Juul; Drucker, Daniel J

    2007-01-01

    to those described for beta-cells, brain and hepatoportal sensors. We determined the role of GLUT2, GLP-1 or GIP receptors in glucose-induced incretins secretion, in the corresponding knockout mice. GLP-1 secretion was reduced in all mutant mice, while GIP secretion did not require GLUT2. Intestinal GLP-1...... content was reduced only in GIP and GLUT2 receptors knockout mice suggesting that this impairment could contribute to the phenotype. Intestinal GIP content was similar in all mice studied. Furthermore, the impaired incretins secretion was associated with a reduced glucose-stimulated insulin secretion...

  5. Autoradiographic studies of the protein metabolism and histochemical demonstration of the zinc content of the brain in diabetic rats. 1

    International Nuclear Information System (INIS)

    Gatzke, H.D.; Wildmeister, W.

    1979-01-01

    Diabetes mellitus was induced in rats by application of streptozotocin: 40 mg/kg body weight streptozotocin produced a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin caused a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals received 308 MBq/animal 3 H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3 H-leucine in different areas of the rat brain were measured. The values of the control animals were compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3 H-leucine values of the diabetic animals were considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3 H-leucine values as well as the zinc content of diabetic animals decreased according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions was discussed. (author)

  6. Effect of different glucose supply conditions on neuronal energy metabolism

    OpenAIRE

    Zheng, Hongwen; Wang, Rubin; Qu, Jingyi

    2016-01-01

    The glucose-excited neurons in brain can sense blood glucose levels and reflect different firing states, which are mainly associated with regulation of blood glucose and energy demand in the brain. In this paper, a new model of glucose-excited neuron in hypothalamus is proposed. The firing properties and energy consumption of this type of neuron under conditions of different glucose levels are simulated and analyzed. The results show that the firing rate and firing duration of the neuron both...

  7. Effect of fitness on glucose, insulin and cortisol responses to diets varying in starch and fat content in Thoroughbred horses with recurrent exertional rhabdomyolysis.

    Science.gov (United States)

    Finno, C J; McKenzie, E; Valberg, S J; Pagan, J

    2010-11-01

    Recurrent exertional rhabdomyolysis (RER) occurs in fit, nervous Thoroughbreds fed high nonstructural carbohydrate (NSC) diets. Clinical signs are diminished by feeding low NSC, high fat diets; however, the mechanism is unclear. To determine if the glucose, insulin and cortisol response to isocaloric diets varying in fat and NSC availability differ in fit vs. unfit Thoroughbreds with RER. Four fit (10 weeks treadmill training) RER Thoroughbred mares were exercised and fed 3 isocaloric (121 MJ/day) diets in a 5 day/diet block design. Two high NSC concentrates, sweet feed (SF) and a processed pelleted feed (PL) and a low starch high fat feed (FAT) were used. After 24 h of rest and a 12 h fast, horses ate half their daily concentrate. Blood sampled for [glucose], [insulin] and [cortisol] was obtained before, immediately after and at 30-60 min intervals for 420 min. After 3-6 months detraining period, the block design was repeated. Results for SF and PL were similar. Regardless of diet, cortisol was higher in fit vs. unfit horses. Fit horses on SF/PL had higher post prandial [insulin] and insulin:glucose ratio than unfit horses. FAT resulted in lower post prandial [glucose] and [insulin] vs. SF/PL. Higher [insulin] in fit vs. unfit horses was not seen on the FAT diet. Increased post prandial [glucose], [insulin] and [cortisol] induced by high NSC, but not high fat, feeds are enhanced by fitness in RER horses. This combination may trigger rhabdomyolysis through increased excitability in RER Thoroughbreds. © 2010 EVJ Ltd.

  8. In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-13C2]glucose.

    Science.gov (United States)

    Lai, Marta; Lanz, Bernard; Poitry-Yamate, Carole; Romero, Jackeline F; Berset, Corina M; Cudalbu, Cristina; Gruetter, Rolf

    2017-01-01

    In vivo 13 C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing 13 C-labeled glucose. Metabolic flux analysis of 13 C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, 13 C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6- 13 C 2 ]glucose for up to 5 h. 13 C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V g  = 0.16 ± 0.03 µmol/g/min) and neurons (V TCA n  = 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V PC  = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V NT  = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR glc ) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from 13 C direct detection with an unprecedented spatial resolution under [1,6- 13 C 2 ]glucose infusion.

  9. An automatic fuzzy-based multi-temporal brain digital subtraction angiography image fusion algorithm using curvelet transform and content selection strategy.

    Science.gov (United States)

    Momeni, Saba; Pourghassem, Hossein

    2014-08-01

    Recently image fusion has prominent role in medical image processing and is useful to diagnose and treat many diseases. Digital subtraction angiography is one of the most applicable imaging to diagnose brain vascular diseases and radiosurgery of brain. This paper proposes an automatic fuzzy-based multi-temporal fusion algorithm for 2-D digital subtraction angiography images. In this algorithm, for blood vessel map extraction, the valuable frames of brain angiography video are automatically determined to form the digital subtraction angiography images based on a novel definition of vessel dispersion generated by injected contrast material. Our proposed fusion scheme contains different fusion methods for high and low frequency contents based on the coefficient characteristic of wrapping second generation of curvelet transform and a novel content selection strategy. Our proposed content selection strategy is defined based on sample correlation of the curvelet transform coefficients. In our proposed fuzzy-based fusion scheme, the selection of curvelet coefficients are optimized by applying weighted averaging and maximum selection rules for the high frequency coefficients. For low frequency coefficients, the maximum selection rule based on local energy criterion is applied to better visual perception. Our proposed fusion algorithm is evaluated on a perfect brain angiography image dataset consisting of one hundred 2-D internal carotid rotational angiography videos. The obtained results demonstrate the effectiveness and efficiency of our proposed fusion algorithm in comparison with common and basic fusion algorithms.

  10. The content of catecholamines in the adrenal glands and sections of the brain under hypokinesia and injection of some neurotropic agents

    Science.gov (United States)

    Melnik, B. E.; Paladiy, E. S.

    1980-01-01

    The dynamics of catecholamine content were studied in the adrenal glands and in various region of the brain of white rats under hypokinesia and injections of neurotropic agents. Profound changes in body catecholamine balance occured as a result of prolonged acute restriction of motor activity. Adrenalin retention increased and noradrenanalin retention decreased in the adrenal glands, hypothalamus, cerebral hemispheres, cerebellum and medulla oblongata. Observed alterations in catecholamine retention varied depending upon the type of neurotropic substance utilized. Mellipramine increased catecholamine retention in the tissues under observation while spasmolytin brought about an increase in adrenalin concentration in the adrenals and a decrease in the brain.

  11. Contributions of Glycogen to Astrocytic Energetics during Brain Activation

    Science.gov (United States)

    Dienel, Gerald A.; Cruz, Nancy F.

    2014-01-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

  12. Contributions of glycogen to astrocytic energetics during brain activation.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2015-02-01

    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

  13. Effects of glucose load on cognitive functions in elderly people

    NARCIS (Netherlands)

    Zwaluw, N.L. van der; Rest, O. van de; Kessels, R.P.C.; Groot, L.C.P.G.M. de

    2015-01-01

    Glucose is the main fuel for the brain, and manipulation of the glucose supply may consequently affect brain function. The present review was conducted to provide an overview of studies that investigated the acute effects of glucose load on memory and other cognitive functions in elderly people. The

  14. Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

    International Nuclear Information System (INIS)

    Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S.

    1990-01-01

    We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

  15. Social stress during adolescence in Wistar rats induces social anxiety in adulthood without affecting brain monoaminergic content and activity

    NARCIS (Netherlands)

    Vidal, Jose; de Bie, Josien; Granneman, Ramon A.; Wallinga, Alinde E.; Koolhaas, Jaap M.; Buwalda, Bauke

    2007-01-01

    Adolescence has been described as an important period to acquire social competences required for adult life. It has been suggested that early stress experiences could affect the development of the brain at different levels. These changes in the brain during adolescence may be related with the

  16. Mining multi-channel EEG for its information content: An ANN-based method for a brain-computer interface

    DEFF Research Database (Denmark)

    Peters, B.O.; Pfurtscheller, G.; Flyvbjerg, H.

    1998-01-01

    . This high recognition rate makes the classifier suitable for a so-called 'Brain-Computer Interface', a system that allows one to control a computer, or another device, with ones brain waves. Our classifier Laplace filters the EEG spatially, but makes use of its entire frequency range, and automatically...

  17. Regulation of Blood Pressure, Appetite, and Glucose by Leptin After Inactivation of Insulin Receptor Substrate 2 Signaling in the Entire Brain or in Proopiomelanocortin Neurons.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Freeman, Nathan J; Alsheik, Ammar J; Adi, Ahmad; Hall, John E

    2016-02-01

    Insulin receptor substrate 2 (IRS2) is one of the 3 major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake, and glucose regulation is unclear. We tested whether genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic, and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure and heart rate and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 μg/kg per minute) for 7 days. Compared with control IRS2(flox/flox) mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 versus 35±1 g and 3.6±0.5 versus 3.8±0.2 g per day) but higher mean arterial pressure (MAP) and heart rate (110±2 versus 102±2 mm Hg and 641±9 versus 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g per day), and had higher MAP and heart rate (108±2 mm Hg and 659±9 bpm) compared with control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2(flox/flox) and in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the central nervous system, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. © 2015 American Heart Association, Inc.

  18. The effect of fish oil supplementation on brain DHA and EPA content and fatty acid profile in mice.

    Science.gov (United States)

    Valentini, Kelly J; Pickens, C Austin; Wiesinger, Jason A; Fenton, Jenifer I

    2017-12-18

    Supplementation with omega-3 (n-3) fatty acids may improve cognitive performance and protect against cognitive decline. However, changes in brain phospholipid fatty acid composition after supplementation with n-3 fatty acids are poorly described. The purpose of this study was to feed increasing n-3 fatty acids and characterise the changes in brain phospholipid fatty acid composition and correlate the changes with red blood cells (RBCs) and plasma in mice. Increasing dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) did not alter brain DHA. Brain EPA increased and total n-6 polyunsaturated fatty acids decreased across treatment groups, and correlated with fatty acid changes in the RBC (r > 0.7). Brain cis-monounsaturated fatty acids oleic and nervonic acid (p acids arachidic, behenic, and lignoceric acid (p acid changes upon increasing n-3 intake should be further investigated to determine their effects on cognition and neurodegenerative disease.

  19. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose......In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  20. Effect of dietary patterns differing in carbohydrate and fat content on blood lipid and glucose profiles based on weight-loss success of breast-cancer survivors.

    Science.gov (United States)

    Thompson, Henry J; Sedlacek, Scot M; Paul, Devchand; Wolfe, Pamela; McGinley, John N; Playdon, Mary C; Daeninck, Elizabeth A; Bartels, Sara N; Wisthoff, Mark R

    2012-01-06

    Healthy body weight is an important factor for prevention of breast cancer recurrence. Yet, weight loss and weight gain are not currently included in clinical-practice guidelines for posttreatment of breast cancer. The work reported addresses one of the questions that must be considered in recommending weight loss to patients: does it matter what diet plan is used, a question of particular importance because breast cancer treatment can increase risk for cardiovascular disease. Women who completed treatment for breast cancer were enrolled in a nonrandomized, controlled study investigating effects of weight loss achieved by using two dietary patterns at the extremes of macronutrient composition, although both diet arms were equivalent in protein: high fat, low carbohydrate versus low fat, high carbohydrate. A nonintervention group served as the control arm; women were assigned to intervention arms based on dietary preferences. During the 6-month weight-loss program, which was menu and recipe defined, participants had monthly clinical visits at which anthropometric data were collected and fasting blood was obtained for safety monitoring for plasma lipid profiles and fasting glucose. Results from 142 participants are reported. Adverse effects on fasting blood lipids or glucose were not observed in either dietary arm. A decrease in fasting glucose was observed with progressive weight loss and was greater in participants who lost more weight, but the effect was not statistically significant, even though it was observed across both diet groups (P = 0.21). Beneficial effects of weight loss on cholesterol (4.7%; P = 0.001), triglycerides (21.8%; P = 0.01), and low-density lipoprotein (LDL) cholesterol (5.8%; P = 0.06) were observed in both groups. For cholesterol (P = 0.07) and LDL cholesterol (P = 0.13), greater reduction trends were seen on the low-fat diet pattern; whereas, for triglycerides (P = 0.01) and high-density lipoprotein (HDL) cholesterol (P = 0.08), a decrease

  1. Intracellular Redox State Revealed by In Vivo 31P MRS Measurement of NAD+ and NADH Contents in Brains

    Science.gov (United States)

    Lu, Ming; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

    2015-01-01

    Purpose Nicotinamide adenine dinucleotide (NAD), in oxidized (NAD+) or reduced (NADH) form, plays key roles in cellular metabolism. Intracellular NAD+/NADH ratio represents the cellular redox state; however, it is difficult to measure in vivo. We report here a novel in vivo 31P MRS method for noninvasive measurement of intracellular NAD concentrations and NAD+/NADH ratio in the brain. Methods It uses a theoretical model to describe the NAD spectral patterns at a given field for quantification. Standard NAD solutions and independent cat brain measurements at 9.4 T and 16.4 T were used to evaluate this method. We also measured T1 values of brain NAD. Results Model simulation and studies of solutions and brains indicate that the proposed method can quantify submillimolar NAD concentrations with reasonable accuracy if adequate 31P MRS signal-to-noise ratio and linewidth were obtained. The NAD concentrations and NAD+/NADH ratio of cat brains measured at 16.4 T and 9.4 T were consistent despite the significantly different T1 values and NAD spectra patterns at two fields. Conclusion This newly established 31P MRS method makes it possible for the first time to noninvasively study the intracellular redox state and its roles in brain functions and diseases, and it can potentially be applied to other organs. PMID:23843330

  2. Variations of blood glucose in cancer patients during chemotherapy

    African Journals Online (AJOL)

    2016-05-23

    May 23, 2016 ... Purpose: The aim of this study was to analyze the blood glucose (BG) variations in cancer patients .... cancer, brain tumor, cervical cancer, and leukemia were the ... excess glucose supply for these glucose‑hungry cells and it.

  3. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    Science.gov (United States)

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  4. Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate.

    Science.gov (United States)

    Pamplona, Reinald; Portero-Otín, Manuel; Sanz, Alberto; Ayala, Victoria; Vasileva, Ekaterina; Barja, Gustavo

    2005-12-01

    What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to mammals of similar body size and metabolic rate. Thus, they are ideal models to identify longevity-related characteristics not linked to body size or low metabolic rates. Since oxidative stress seems to be related to the basic aging process, we measured specific markers of different kinds of oxidative damage to proteins, like glutamic and aminoadipic semialdehydes (GSA and AASA, specific protein carbonyls), Nɛ-(carboxyethyl)lysine (CEL), Nɛ-(carboxymethyl)lysine (CML), and Nɛ-(malondialdehyde)lysine (MDAL), as well as mitochondrial Complex I content and amino acid and membrane fatty acyl composition, in the brain of short-lived mice (maximum life span [MLSP] 3.5 years) compared with those of long-lived budgerigar 'parakeets' (MLSP, 21 years) and canaries (MLSP, 24 years). The brains of both bird species had significantly lower levels of compounds formed as a result of oxidative (GSA and AASA), glycoxidative (CEL and CML), and lipoxidative (CML and MDAL) protein modifications, as well as a lower levels of mitochondrial complex I protein. Although it is known that fatty acid unsaturation is lower in many tissues of long-lived compared to short-lived mammals, this is not true in the particular case of brain. In agreement with this, we also found that the brain tissue of bugerigars and canaries contains no fewer double bonds than that of mice. Amino acid composition analyses revealed that bird proteins have a significantly lower content of His, Leu and Phe, as well as, interestingly, of methionine, whereas Asp, Glu, Ala, Val, and Lys contents were higher than in the mammals. These results, together with those previously described in other tissues of pigeons (MLSP, 35 years) compared to rats (MLSP, 4 years), indicate that oxidative damage to proteins, lipids and mitochondrial DNA are lower in birds (very

  5. A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals.

    Science.gov (United States)

    Bamatraf, Saeed; Hussain, Muhammad; Aboalsamh, Hatim; Qazi, Emad-Ul-Haq; Malik, Amir Saeed; Amin, Hafeez Ullah; Mathkour, Hassan; Muhammad, Ghulam; Imran, Hafiz Muhammad

    2016-01-01

    We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG) brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM) and long term memory (LTM) and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM) which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM) and two months (LTM), and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM.

  6. Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate

    Science.gov (United States)

    Deelchand, Dinesh K.; Nelson, Christopher; Shestov, Alexander A.; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2009-02-01

    In this work the feasibility of measuring neuronal-glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate was investigated. Time courses of 13C spectra were measured in vivo while infusing both 13C-labeled substrates simultaneously. Individual 13C isotopomers (singlets and multiplets observed in 13C spectra) were quantified automatically using LCModel. The distinct 13C spectral pattern observed in glutamate and glutamine directly reflected the fact that glucose was metabolized primarily in the neuronal compartment and acetate in the glial compartment. Time courses of concentration of singly and multiply-labeled isotopomers of glutamate and glutamine were obtained with a temporal resolution of 11 min. Although dynamic metabolic modeling of these 13C isotopomer data will require further work and is not reported here, we expect that these new data will allow more precise determination of metabolic rates as is currently possible when using either glucose or acetate as the sole 13C-labeled substrate.

  7. Distribution of the insecticide 14 C-fen valerate and its effect on protein and amino acid content in different brain areas of the rat

    International Nuclear Information System (INIS)

    Aly, M.A.S.

    1998-01-01

    Intragastric administration of fenvalerate (45 mg/kg) to male rats induced symptoms associated with gamma-cyano pyrethroids (type II syndrome). Fenvalerate crossed blood brain barrier and reached different brain areas. The highest concentration of fenvalerate was found in striatum (18.7+2.5 Mou/g) followed by pons + medulla oblongata (10.4+ 0.91Moug/g) after 24 h of the insecticide administration. A decrease in the protein content in different brain areas was recorded at 24 h. However, it was observed that there was a tendency for the protein level to recover at 48 h although it was still lower than corresponding controlgroup. Excitatory neurotransmitter amino acids, glutamic and aspartic, in the pons + medulla oblongata showed a prominent decrease (-9.9 and 7.0%, respectively). Inhibitory neurotransmitter amino acids, glycine and alanine, showed a slight decrease. On the other hand, the amino acids in the striatum revealed fluctuating changes. Amino acids acting as a precursor of neurotransmitter were also affected in the selected brain areas. The data obtained revealed that fenvalerate caused subtle disruption in the integrity of the CNS and there is a possibility that such disruption might result in physiological and behavioural alteration which may affect the organism ability to interact with environment

  8. Effects of glucose and sucrose on mood: a systematic review of interventional studies

    NARCIS (Netherlands)

    Rest, van de O.; Zwaluw, van der N.L.; Groot, de C.P.G.M.

    2018-01-01

    Context: Glucose is the main energy source for the brain, and as such, manipulation of glucose supply may affect brain function. It has been suggested that a change in blood glucose may influence mood. Objective: The aim of this review was to investigate the potential effects of glucose and sucrose,

  9. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    International Nuclear Information System (INIS)

    Beck, T.; Krieglstein, J.

    1987-01-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O 2 . Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded [ 14 C]2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur

  10. Adenosinetriphosphate content and adenosinetriphosphatase activity in cell fractions of the liver and brain of chick embryos and birds treated with gamma-rays

    International Nuclear Information System (INIS)

    Todorov, B.

    1977-01-01

    Studies are conducted on the level of ADP and the adenosinetriphosphatase in nuclei, mitochondria, and microsomes taken from the brain and liver of singly gamma-irradiated (1000 rd) chick embryos and birds. As a result of the treatment the ADP content dropped, while the activity of ADP rose. These changes were more strongly expressed in the nuclei, than in the mitochondria, and to a lesser extent - in the microsomes. Twelve-day chick embryos showed more markedly expressed radiosensitivity than newly hatched chicks. This embryonal stage is characterized by intense growth, differentiation and metabolic processes in the liver, which substantiate not only the higher radiosensitivity of this age group but the more strongly expressed changes in the liver as compared with the brain. (author)

  11. Content-based retrieval of brain tumor in contrast-enhanced MRI images using tumor margin information and learned distance metric.

    Science.gov (United States)

    Yang, Wei; Feng, Qianjin; Yu, Mei; Lu, Zhentai; Gao, Yang; Xu, Yikai; Chen, Wufan

    2012-11-01

    A content-based image retrieval (CBIR) method for T1-weighted contrast-enhanced MRI (CE-MRI) images of brain tumors is presented for diagnosis aid. The method is thoroughly evaluated on a large image dataset. Using the tumor region as a query, the authors' CBIR system attempts to retrieve tumors of the same pathological category. Aside from commonly used features such as intensity, texture, and shape features, the authors use a margin information descriptor (MID), which is capable of describing the characteristics of tissue surrounding a tumor, for representing image contents. In addition, the authors designed a distance metric learning algorithm called Maximum mean average Precision Projection (MPP) to maximize the smooth approximated mean average precision (mAP) to optimize retrieval performance. The effectiveness of MID and MPP algorithms was evaluated using a brain CE-MRI dataset consisting of 3108 2D scans acquired from 235 patients with three categories of brain tumors (meningioma, glioma, and pituitary tumor). By combining MID and other features, the mAP of retrieval increased by more than 6% with the learned distance metrics. The distance metric learned by MPP significantly outperformed the other two existing distance metric learning methods in terms of mAP. The CBIR system using the proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10 images were returned by the system. Compared with scale-invariant feature transform, the MID, which uses the intensity profile as descriptor, achieves better retrieval performance. Incorporating tumor margin information represented by MID with the distance metric learned by the MPP algorithm can substantially improve the retrieval performance for brain tumors in CE-MRI.

  12. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons.

    Science.gov (United States)

    Lund, Trine M; Risa, Oystein; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2009-07-01

    Ketone bodies serve as alternative energy substrates for the brain in cases of low glucose availability such as during starvation or in patients treated with a ketogenic diet. The ketone bodies are metabolized via a distinct pathway confined to the mitochondria. We have compared metabolism of [2,4-(13)C]beta-hydroxybutyrate to that of [1,6-(13)C]glucose in cultured glutamatergic neurons and investigated the effect of neuronal activity focusing on the aspartate-glutamate homeostasis, an essential component of the excitatory activity in the brain. The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. Our results suggest that the change in aspartate-glutamate homeostasis is due to a decreased availability of NADH for cytosolic malate dehydrogenase and thus reduced malate-aspartate shuttle activity in neurons using beta-hydroxybutyrate. In the presence of glucose, the glutamate content decreased significantly upon activation of neurotransmitter release, whereas in the presence of only beta-hydroxybutyrate, no decrease in the glutamate content was observed. Thus, the fraction of the glutamate pool available for transmitter release was diminished when metabolizing beta-hydroxybutyrate, which is in line with the hypothesis of formation of transmitter glutamate via an obligatory involvement of the malate-aspartate shuttle.

  13. Depletion of intracellular polyamine content does not alter the survival of 9L rat brain tumour cells after X-irradiation

    International Nuclear Information System (INIS)

    Seidenfeld, J.; Deen, D.F.; Marton, L.J.

    1980-01-01

    A 24-hour preincubation of 9L rat brain tumour cells with 10 mM DL-α methylornithine (αMO) reduced 9L putrescine content by more than 97%, spermidine content by 67% and total polyamine content by 50%. This did not increase the sensitivity of 9L cells to killing by X-rays. Polyamine content of treated and untreated cells did not vary with X-ray dose. A similar experiment was performed with 9L cells incubated for 48 hours in the presence and absence of 25 mM DL-α-difluoromethylornithine (DFMO). X-ray dose again did not affect polyamine contents of either DFMO treated or untreated cells. The reduction of total polyamine content by 75% produced by this treatment did not affect the X-ray dose-response curve of 9L cells. Incubation of 9L cells with 40 μM methylglyoxal bis (guanylhydrazone) (MGBG) for 48 hours also did not increase the sensitivity of the treated cells to killing by X-rays. Measurement of intracellular polyamine contents for MGBG-treated and untreated cell showed that Sd was reduced by 70% and Sp by 66%. The increase in Pu content resulted in equal total polyamine contents on a molar basis for both groups of cells. Cultures of 9L cells were incubated for 48 hours in the presence or absence of 40 μM MGBG + 25 mM DFMO, producing an 87% reduction in to