Glucose Utilization In Rat Brain Research Articles

In vivo mapping of temporospatial changes in glucose utilization in rat brain during epileptogenesis: an 18F-fluorodeoxyglucose–small animal positron emission tomography study

Cerebral glucose hypometabolism is common in temporal lobe epilepsy (TLE). The temporospatial evolution of these metabolic changes during epileptogenesis remains to be determined. We measured the regional normalized cerebral metabolic rate for glucose (nCMRglc) with 18F-fluorodeoxyglucose (FDG)–small animal positron emission tomography (microPET) in animals receiving systemic pilocarpine application. The microPET scan was performed on day 2 (early), day 7 (latent) and 42 days (chronic phase) after the initial status epilepticus. We found specific temporospatial changes in glucose utilization in rats during the course of epileptogenesis. In the early phase, the limbic structures underwent the largest decrease in glucose utilization. Most brain structures were still hypometabolic in the latent phase and recovered in the chronic phase. Conversely, the hippocampus and thalamus presented with persistent hypometabolism during epileptogenesis. The cerebellum and pons maintained normal glucose utilization during this process. We also found that severe glucose hypometabolism in the entorhinal cortex during the early phase was correlated with epileptogenesis, indicating the critical role of the entorhinal cortex in the early stages of TLE.

Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels.

The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.

Glucose transporters and glucose utilization in rat brain after acute ethanol administration.

In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline i.p. 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 +/- 8.9 Vs 91 +/- 8.9 pmoles/mg protein (p < 0.05 N=4) and the estimated Kd values were 0.37 +/- 0.03 and 0.28 +/- 0.05 microM (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUTI and 54% and 21% (p<0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMR(Glc)) was studied using [6-(14)C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol in-vivo decrease GLUT number and protein content in rat cerebral cortex.

Increase in glucose transporter densities of Glut3 and decrease of glucose utilization in rat brain after one week of hypoglycemia

The present study addresses the question whether a chronic decrease of plasma glucose concentration for 1 week induces a global or local increase in glucose transporter densities Glut1 and Glut3 in the brain. To induce chronic hypoglycemia insulin was infused into rats by osmotic minipumps for 1 week resulting in a mean plasma glucose concentration of 3.1±0.5 mmol/l (control group: 8.1±0.5 mmol/l). Global and local densities of Glut1 and Glut3 glucose transporters were measured by immunoautoradiographic methods. The mean density of glucose transporters Glut1 remained unchanged, whereas the mean density of Glut3 increased slightly, although significantly. To determine whether the increased density of Glut3 is related to a change in glucose metabolism, the local cerebral metabolic rate of glucose (lCMR glc) was quantified by the 2-deoxyglucose method. Mean glucose utilization was decreased by 15%. Local analysis of transporter densities (Glut1 and Glut3) and glucose utilization showed a significant correlation between local glucose transporter densities (Glut1 and Glut3) and lCMR glc during hypoglycemia as already previously observed during normoglycemia. It is concluded that 1 week of hypoglycemia is a stimulus for the induction of additional glucose transporters Glut3 in the brain. These additional neuronal glucose transporters may support the maintenance of glucose utilization which is not completely maintained under these conditions.

Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain

The effects of diazepam, which acts at GABAA receptors to enhance the effects of GABA, and ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, on local rates of cerebral glucose utilization (ICMRglc) were examined in unrestrained rats. Four groups were studied: vehicle-injected controls; and ketamine-treated, diazepam-treated and combined ketamine- and diazepam-treated animals. Ketamine alone produced a heterogeneous pattern of changes in ICMRglc (e.g. significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system). Diazepam alone statistically significantly decreased ICMRglc in the brain as a whole and in most areas of the cerebral cortex, thalamus and limbic system. The most remarkable effects of the two drugs administered together on ICMRglc occurred in the limbic system where the dramatic increases observed with ketamine alone were prevented by treatment with diazepam.

Alteration of local cerebral glucose utilization following intravenous administration of heroin in Fischer 344 rats

The 2-deoxyglucose method was used to study the effects of acute administration of small intravenous doses of heroin on rates of glucose utilization in rat brain to identify small brain regions that may be involved in the acute behavioral effects of heroin. In contrast to previous studies which have used relatively large doses, the doses of heroin used in this study have been shown to be self-administered [Martin, T.J., Dworkin, S.I. and Smith, J.E., Alkylation of μ-opioid receptors by β-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats., J. Pharmacol. Exp. Ther., 272 (1995) 1135–1140.]. Administration of 18 μg/kg of heroin resulted in higher rates of glucose utilization in the medial olfactory tubercle, anterior nucleus accumbens and dorsolateral caudate while having no other effects on limbic structures compared to saline-treated animals. Conversely, the rate of glucose utilization was lower than control in the habenula, dorsal raphe, and central gray following adminstration of 18 μg/kg of heroin. Administration of two higher doses (60 and 100 μg/kg) resulted in lower rates of glucose utilization in the thalamus, habenula, inferior colliculus, dorsal raphe and central gray compared to saline. The higher rates of glucose utilization in the limbic areas were specific for the lowest dose of heroin, whereas the effect of lowering the rate of glucose utilization compared to control in the thalamus and inferior colliculus were an increasing function of dose. In the habenula and dorsal raphe, however, the dose-effect function was inverted. These data indicate that the alterations of glucose utilization in rat brain by heroin are site-specific and the systems involved as well as the nature of the alteration differs for individual doses of heroin.

Comparative study of dopamine metabolism with local cerebral glucose utilization in rat brain following the administration of haloperidol decanoate

The effects of haloperidol decanoate on dopamine (DA) metabolism in discrete regions of rat brain were investigated and compared with changes in local cerebral glucose utilization (LCGU). The concentration of DA and its metabolite, homovanillic acid, and the α-methyl- p-tyrosine (α-MT)-induced decline of DA were measured in 6 brain regions by a high-performance liquid chromatographic assay. LCGU in 26 brain regions were examined by 14C]2-deoxy-D-glucose autoradiography. At 24-hr after intramuscular injection of haloperidol decanoate (60 mg eq/kg to haloperidol), the concentration of homovanillic acid in the prefrontal cortex, caudate-putamen, accumbens nucleus, lateral amygdala, and medial thalamus showed significant increase compared with control values. On day 21, the increase in these regions was significantly attenuated with no significant difference from the controls Furthermore, chronic haloperidol rats showed α-MT-induced decline of DA to a similar extent in the control rats. LCGU on day 21 showed significant decrease in the parietal cortex, and a tendency toward decrease in the prefrontal cortex, lateral amygdala and medial thalamus compared with the controls. There was no significant change in LCGU in the caudate-putamen or accumbens nucleus. Chronic haloperidol would thus appear to affect energy metabolism mainly in the cortico-thalamo-limbic circuits, and this may not correspond well to presynaptic DA metabolism.

Distribution of effects of the κ-opioid agonist CI-977 on cerebral glucose utilization in rat brain

The effects of the κ-opioid agonist CI-977 upon local cerebral glucose utilization have been examined in conscious, lightly restrained rats to gain insight into the potential adverse effects of this neuroprotective agent. Cerebral glucose utilization was assessed quantitatively in 45 anatomically discrete brain regions by means of [ 14C]2-deoxyglucose autoradiography. The i.v. administration of CI-977 (0.03–3 mg/kg) induced relatively homogeneous patterns of altered cerebral glucose utilization with moderate statistically significant reductions (∼ 25%) being observed in 29 brain regions, and a statistically significant increase (∼ 40%) in obe brain region, the lateral habenular nucleus. Glucose use throughout the entire neocortex and inferior colliculus was particularly sensitive to reduction (∼ 35%) following CI-977 administration, although there was only a limited dose dependency to the response. Minimal alterations in glucose use were observed in 15 of the 45 brain regions, particularly in the lower brain stem (e.g. superior olives, cochlear nucleus and median raphe) and forebrain limbic regions (e.g. septal nucleus, nucleus accumbens and mediodorsal thalamus). These data demonstrate that CI-977 produced widespread, anatomically organized alterations in function-related glucose use which contrast those seen previously with the NMDA receptor antagonists, thereby suggesting that CI-977 may be intrinsically safer as an in vitro neuroprotective agent.

Effect of vanadium on regional brain glucose utilization in rats

Recent study has indicated that administration of vanadate, an insulomimetic agent, stimulates glucose uptake in the brain, concurrently with a suppression of food intake. The present work was carried out to characterize which specific brain areas are implicated in this increased glucose utilization. After 3 days of vanadate or vanadyl treatment, anaesthetized fasted rats were injected with tritiated 2-deoxyglucose and different brain areas were punched. Vanadate had no effect on glucose utilization but vanadyl significantly increased glucose uptake in the olfactory bulbs, the hypothalamus, and the hindbrain compared to the pair fed controls.

The effects of chronic serum sickness on albumin distribution and glucose utilization in rat brain

The level of cerebrospinal fluid (CSF) protein is elevated in diseases and disease models that are associated with circulating immune complexes such as serum sickness. Circulatory immune complexes are known to deposit in the basal lamina of fenestrated capillaries and may, as a result, affect both capillary bed and parenchymal function. Since the brain has both fenestrated and unfenestrated capillaries and immune complexes deposit to a varying extent in the fenestrated capillaries in chronic serum sickness, cerebral capillary permeability to protein may be altered in some brain areas and lead to the elevation of CSF proteins. In addition various other cerebrovascular and metabolic functions may also be affected by this condition. In this study either radio-iodinated serum albumin (RISA) or 2-[14C]deoxyglucose (14C-2DG) was intravenously injected into control Wistar rats and Wistar rats with chronic serum sickness; subsequently the tissue levels of radioactivity were measured by quantitative autoradiography in 4 brain areas with fenestrated capillaries and 11 brain areas with unfenestrated capillaries. The 2-min distribution of RISA, which demarcates the volume of circulating plasma in perfused microvessels and is generally proportional to local plasma flow, was the same in control and experimental rats. The passage of RISA from blood into brain over 30 min was negligible in both groups; thus cerebral capillary permeability to albumin was not detectably increased in any of these 15 brain areas by chronic serum sickness. The rate of local cerebral glucose utilization, an indicator of local metabolic and neural activity, was calculated from the 14C-2DG data and was virtually identical in control and experimental rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral glucose utilization in rat brain during phenobarbital withdrawal

The phenobarbital withdrawal syndrome in rats is characterized by tremors, arched back, weight loss and hyperactivity. This syndrome is shown to be associated with both general and localized increases in cerebral glucose utilization. An increase in glucose utilization (significant at the P ⩽ 0.001 level) was observed in 72 % of the 57 structures examined. Increases in glucose utilization of ≥ 180% of control values were noted in structures associated with the motor system (columns in the frontal sensorimotor cortex, globus pallidus, dentate nucleus of the cerebellum and ovoid areas in the cerebellar vermis), thalamic nuclei (lateral and posterior), dorsal lateral geniculate, mammillary body, cingulate cortex, locus coruleus, and cerebellar flocculus and paraflocculus. The structures showing the greatest increase in glucose utilization were cerebellar paraflocculus (257% of control), columns in the frontal sensorimotor cortex (247% of control) and avoid areas in the cerebellar vermis (223% of control). Areas of the brain that have been described as cell body areas for serotonergic (raphe), noradrenergic (locus ceruleus), dopaminergic (substantia nigra, zona compacta) and GABAergic (globus pallidus) neurons also showed increases in glucose utilization. The pattern of cerebral glucose utilization accompanying the phenobarbital withdrawal syndrome in rats contrasts with that for morphine withdrawal and exhibits both similarities and differences with respect to ethanol withdrawal.

Metabolic mapping of functional activity in rat brain and pituitary after water deprivation.

Glucose utilization in rat brain and pituitary was measured in control and water-deprived rats by autoradiographic assessment of the metabolic trapping of radioactivity from [1-14C]glucose. Two days of water deprivation resulted in significant increases in hematocrit, plasma osmolality and vasopressin levels, indicating a functional activation of magnocellular vasopressin neurons. The uptake and retention of radioactivity from [1-14C]glucose in the dehydrated rats, compared to controls, was 103% greater in the magnocellular portion of the paraventricular nucleus and 74% greater in the supraoptic nucleus. Water deprivation also resulted in significant increases in glucose utilization (30-40%) in the lateral and anterior hypothalamic areas, somatosensory cortex and cingulate cortex. No change in glucose utilization after 2 days of water deprivation was apparent in the parvocellular paraventricular nucleus, periventricular nucleus of the hypothalamus, corpus callosum, organum vasculosum of the lamina terminalis (OVLT) or the subfornical organ (SFO). In the pituitary, glucose utilization was increased in the neural lobe but was unchanged in the anterior and intermediate lobes after water deprivation. Under the conditions of the present study, no increase in metabolic activity was apparent in 2 brain regions thought to be possible sources of osmoreception, the OVLT and SFO. These results do not support, but do not exclude, functional involvement of the OVLT and SFO in regulating the activity of magnocellular neurons of the paraventricular nucleus and supraoptic nucleus during chronic water deprivation.

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

The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [14C]-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.

Regional brain glucose utilization in rats during etomidate anesthesia.

The influence of etomidate on regional cerebral function as reflected by regional cerebral glucose utilization (rCMRGlc) was studied. Three experiments were performed. In the first, rats had both left femoral vessels cannulated and were placed in restraining cages. Etomidate was infused intravenously (12 mg/kg) at a rate of 6 mg X kg-1 X min-1. This large dose had a modest effect on blood pressure and heart rate, which could be explained by the elimination of stress in restrained rats, and no effect on body temperature, Pao2, PaCo2, or pH. A second group of rats were used to determine the effect of etomidate on the ratio of brain glucose to plasma glucose, which is necessary for calculating rCMRGlc. In the third experiment rCMRGlc was measured in unstressed rats. The rats were anesthetized with an intravenous dose of 1, 2, 6, or 12 mg/kg etomidate infused at a rate of 6 mg X kg-1 X min-1. Etomidate had a marked effect on glucose consumption in many, but not all, cerebral structures. The forebrain (telencephalon and diencephalon) was most affected (-25% to -35%) while the hindbrain was minimally affected. There was no demonstrable dose dependency; 1 mg/kg depressed rCMRGlc as much as 12 mg/kg. The pattern of rCMRGlc depression is in accord with the minimal effects observed on physiologic variables and similar to that caused by the steroid anesthetic Althesin, although the depression seen was not as severe. The pattern of metabolic depression produced by etomidate differs markedly from that produced by barbiturates, which affect all brain regions to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

The regional distribution of d-amphetamine and local glucose utilization in rat brain during continuous amphetamine administration.

The distribution of radioactivity following administration of either [3H]d-ampetamine or [3H]2-deoxy-d-glucose was examined by scintillation counting of 22 microdissected brain regions from rats pretreated with either acute or continuous amphetamine, or continuously administered labeled d-amphetamine. Animals continuously administered drug were sacrificed in behaviorally distinct stages of the continuous amphetamine syndrome, a potential animal model of amphetamine psychosis. Both isotopes were heterogeneously distributed within brain, and their distributions were differentially affected by acute or continuous amphetamine regimens. While the distribution of either isotope in naive rats was characterized by greatest concentrations of counts in rostral rather than caudal regions, and grey-matter rather than white-matter structures, continuous amphetamine administration resulted in progressively increased retention of amphetamine by mesolimbic but not nigrostriatal brain regions; this was accompanied by locally enhanced levels of glucose utilization. This effect was predominantly localized in the nucleus accumbens, which exhibited the greatest retention of amphetamine and greatest relative increase in glucose utilization of any region studied during that stage of the continuous amphetamine syndrome thought to best model amphetamine psychosis. Alterations in amphetamine distribution and local levels of neural activity may reflect a change in the principal locus of control of amphetamine effects within brain as animals progress through the stages of the continuous amphetamine syndrome.

Regional changes in brain glucose utilization in rats given a pyrethroid insecticide

Regional changes in brain glucose utilization in rats given a pyrethroid insecticide

Effects of Ethanol on Glucose Utilization in Rat Brain

SummarySigns of impairment of utiliztion of glucose in rat brains at 2 1/2 hr after administration of ethanol included increased glucose ratios for cerebrum/blood and hind-brain/blood in fed and fasted rats, decreased concentrations of lactate in cerebrum and hindbrain in fed rats, higher percentages of brain 14C in glucose at 15 min after injection of glucose-U-14C, and decreases in blood glucose equivalents in the combined glucose metabolites in cerebrum and hindbrain of fed and fasted rats.Glucose uptake in cerebrum and hindbrain was lower in rats given ethanol by stomach tube (fed or fasted) than in control rats. Glucose uptake was normal in fed rats given ethanol intraperitoneally, but they had increased blood glucose concentrations. However, in these rats with the greater supply of blood glucose the greatest decreases in blood glucose equivalents of brain glucose metabolites were found. Significant decreases were found in aspartate, glutamate, glutamine, and γ-aminobutyrate (GABA).Effects of fasting...

RATE OF UTILIZATION OF GLUCOSE AND 'COMPARTMENTATION' OF ALPHA-OXOGLUTARATE AND GLUTAMATE IN RAT BRAIN.

1. The rate of incorporation of (14)C into pyruvate, alpha-oxoglutarate, lactate and glucose of rat tissues was measured after the subcutaneous injection of uniformly labelled glucose. 2. In rat brain the specific radioactivities of lactate and glucose were similar to that of alanine. In liver the specific radioactivity of glucose was considerably higher than that of lactate or alanine. 3. The specific radioactivities of alpha-oxo acids of rat brain were lower than those of corresponding amino acids, alanine and glutamate. These findings have been explained in relation to metabolic compartments in vivo. 4. The approximate estimated rate of glucose utilization in rat brain in vivo is 0.96mumole/g. of brain/min.