2DG Uptake Research Articles

Regulation of the glucose:H+ symporter by metabolite-activated ATP-dependent phosphorylation of HPr in Lactobacillus brevis

Lactobacillus brevis takes up glucose and the nonmetabolizable glucose analog 2-deoxyglucose (2DG), as well as lactose and the nonmetabolizable lactose analoge thiomethyl beta-galactoside (TMG), via proton symport. Our earlier studies showed that TMG, previously accumulated in L. brevis cells via the lactose:H+ symporter, rapidly effluxes from L. brevis cells or vesicles upon addition of glucose and that glucose inhibits further accumulation of TMG. This regulation was shown to be mediated by a metabolite-activated protein kinase that phosphorylase serine 46 in the HPr protein. We have now analyzed the regulation of 2DG uptake and efflux and compared it with that of TMG. Uptake of 2DG was dependent on an energy source, effectively provided by intravesicular ATP or by extravesicular arginine which provides ATP via an ATP-generating system involving the arginine deiminase pathway. 2DG uptake into these vesicles was not inhibited, and preaccumulated 2DG did not efflux from them upon electroporation of fructose 1,6-diphosphate or gluconate 6-phosphate into the vesicles. Intravesicular but not extravesicular wild-type or H15A mutant HPr of Bacillus subtilis promoted inhibition (53 and 46%, respectively) of the permease in the presence of these metabolites. Counterflow experiments indicated that inhibition of 2DG uptake is due to the partial uncoupling of proton symport from sugar transport. Intravesicular S46A mutant HPr could not promote regulation of glucose permease activity when electroporated into the vesicles with or without the phosphorylated metabolites, but the S46D mutant protein promoted regulation, even in the absence of a metabolite. The Vmax but not the Km values for both TMG and 2DG uptake were affected. Uptake of the natural, metabolizable substrates of the lactose, glucose, mannose, and ribose permeases was inhibited by wild-type HPr in the presence of fructose 1,6-diphosphate or by S46D mutant HPr. These results establish that HPr serine phosphorylation by the ATP-dependent, metabolite-activated HPr kinase regulates glucose and lactose permease activities in L. brevis and suggest that other permeases may also be subject to this mode of regulation.

Quantitative autoradiographic measurement of cocaine-induced regional myocardial metabolic changes in hypertensive rats

A rat model of hypertensive cardiomyopathy was studied to evaluate the acute effects of cocaine on the myocardium. Using autoradiographic microimaging techniques, myocardial perfusion ( 201Tl) and energy substrate utilization (glucose: [ 14C]2-fluoro-2-deoxy- d-glucose—[ 14C]2DG and fatty acid (15-[ p-iodophenyl]) -3- R,S-methyl pentadecanoic acid—[ 131I]BMIPP) were studied in Dahl strain salt-sensitive normotensive and hypertensive rats with and without intravenous cocaine. The right ventricle, septum, endocardium and epicardium of the left ventricle were analyzed. Increased perfusion (18%) was seen in the myocardium of the hypertensive rats as compared to the normotensive rats. There was higher [ 14C]2DG (254%) and lower fatty acid (13.2%) uptake in the hypertensive rats, indicative of a shift from aerobic to anaerobic substrate utilization. In cocaine-treated normotensive rats, a generalized decrease in myocardial perfusion (30%) and increased glucose metabolism (89%) was seen. In cocaine-treated hypertensive rats, the increased myocardial perfusion (16%) was heterogeneous and was more pronounced in septum and epicardium. The endocardium and epicardium in the hypertensive rats showed an overall increase (23%) in glucose utilization after cocaine which was not as dramatic as was seen in the normotensive heart and a slight increase in fatty acid utilization. These results are consistent with prior observations that under pressure overload the myocardium responds non-uniformly. It may well be that the hypertensive cardiomyopathic heart is unable to respond to the challenge of cocaine by further increasing glucose utilization. These data obtained in an animal model of hypertension seem to indicate that hypertension may increase the risk of cardiac complications related to cocaine.

Pineal regulation of circadian rhythms of 2-deoxy[14C]glucose uptake and 2[125I]iodomelatonin binding in the visual system of the house sparrow,Passer domesticus

The pineal gland and its hormone melatonin are crucial for the generation of circadian rhythms in several species of passerine birds. The sites and mechanisms by which they influence avian behavior are therefore of particular interest. Recent research employing several brain imaging techniques has indicated that the sites of melatonin action within the avian brain are wide-spread within the 4 major visual pathways. In this study, we have investigated whether the avian homologue of the mammalian suprachiasmatic nucleus, the visual suprachiasmatic nucleus (vSCN), and other visually sensitive structures express circadian rhythms of 2-deoxy[14C]glucose (2DG) uptake and 2[125I]iodomelatonin (IMEL) binding in house sparrows,Passer domesticus, under constant environmental conditions in the presence or absence of the pineal gland. The results indicate that 2DG uptake in the vSCN is oscillatory in sham-operated sparrows but damps to arrhythmicity in pinealectomized birds, suggesting this structure contains a damped circadian oscillator independent of pineal input. We have also asked whether IMEL binding is rhythmic under these conditions in the same brains. These results indicate IMEL binding is rhythmic in several structures in the circadian, tectofugal, thalamofugal visual pathways and that pinealectomy increases the level of IMEL binding 2–4 fold suggesting that IMEL binding is down regulated by endogenous melatonin. However, the circadian rhythm of this binding is only gradually abolished, suggesting it too is regulated by a non-pineal circadian clock. These data are discussed in the context of the behavioral neurobiology of avian circadian systems and the neuroendocrine loop model.

Daily melatonin administration synchronizes circadian patterns of brain metabolism and behavior in pinealectomized house sparrows,Passer domesticus

Recent research in our laboratory has indicated that in sparrows the visual suprachiasmatic nucleus (vSCN) is metabolically rhythmic such that 2-deoxy[14C]glucose (2DG) uptake and specific binding of 2[125I]iodomelatonin (IMEL) are high during subjective day for up to 10 circadian cycles in constant darkness (DD). These rhythms damp to arrhythmicity in pinealectomized birds (PINX). The present study was designed to test the hypothesis that exogenous melatonin rhythmically applied can restore disrupted behavioral and cerebral rhythmicity. Pinealectomized house sparrows were placed in constant dim light and allowed to become arrhythmic. Experimental birds received 0.86 mM melatonin in 0.01% ethanol (ETOH) to drink for 12 of every 24 h for 14 days. Control birds received 0.01% ETOH only. Behavioral rhythmicity was restored by melatonin but not by ETOH. Birds were injected with 2DG 6 or 18 h following the beginning of melatonin (for experimental birds: MT06 and MT18 respectively) or ETOH (for control birds: ET06 and ET18 respectively) administration, allowed to survive 1 h and killed for 2DG and IMEL autoradiography. The data indicated 2DG rhythmicity such that uptake was high at MT18 in vSCN and several visual, auditory and limbic system structures in birds receiving melatonin but not in birds receiving ETOH. Similarly, IMEL binding rhythms were restored in vSCN and other visual, auditory and limbic system structures in birds receiving melatonin but not in those receiving ETOH. These data indicate that melatonin cycles are responsible for generating and/or driving a wide array of cerebral metabolic rhythms and that this influence is inhibitory.

Development of metabolic activity patterns in the somatosensory cortex of cats

1. The development of cortical responses to somatic stimulation was studied in kittens 2-5 wk of age using the 2-deoxyglucose (2DG) technique. During the 2DG experiment each kitten received an innocuous intermittent vertical displacement stimulus to the forepaw. 2. The pattern of metabolic activity was substantially different in young animals compared with adults. In the individual autoradiographs of the 2-wk-old kittens stimulus-evoked 2DG uptake in primary somatosensory cortex was localized to a small spot in the upper portion of the cortex, whereas in the adult the label extended vertically through the cortical layers and appeared more column-like. Individual patches of label were substantially smaller and less dense in young animals. Over a period of several weeks the evoked activity evolved to the more extensive adult pattern. The 2DG uptake displayed a mature distribution by approximately 4-5 wk of age. During this period, the cortical architecture also evolved from an immature to a mature arrangement. 3. The evoked activity was reconstructed into two-dimensional maps; the distribution of label > or = 1.5 SD above background was considered to be stimulus related. In the adult, the pattern appeared as a strip or strips of increased metabolic activity that extended in the rostrocaudal direction for approximately 1 mm. In contrast, the activity pattern in animals 2-4 wk old was less discretely organized into "strips" and was more diffusely spread over several mms of somatosensory cortex. The two-dimensional pattern gradually coalesced into a more localized strip by approximately 4-5 wk of age. Although the pattern of label was more widespread in the young animals, the absolute distance of the spread of activity did not vary substantially, regardless of the age of the animal. 4. Other measurements regarding the distribution of activity at different ages indicate that the amount of cortex activated increases in absolute terms, although the percent of cortex activated by the stimulus decreases. The overall intensity of the 2DG uptake as measured on the two-dimensional maps increases with age, as does the variability of the 2DG uptake; a wider range of intensity values is seen in the adult. Plots created from the individual two-dimensional reconstructions allowed a measure of "patch strength" at different ages. These histograms relate the most intense region of uptake in a given map to the spatial distribution of activity spreading in the medial and lateral directions.(ABSTRACT TRUNCATED AT 400 WORDS)

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Arachidonic acid (AA) has recently been shown to influence various cellular functions in the central nervous system. Here we report that AA increases, in a time- and concentration-dependent manner, 2-deoxy-D-[1-3H]glucose ([3H]2DG) uptake in primary cultures of astrocytes prepared from the cerebral cortex of neonatal mice. This effect is mimicked by an unsaturated fatty acid such as linolenic acid, while palmitic and arachidic acids, two saturated fatty acids, are inactive. Pharmacological agents that increase the endogenous levels of AA by stimulating AA release (melittin) or by inhibiting its reacylation (thimerosal) also promote [3H]2DG uptake by astrocytes. We also report that norepinephrine (NE) stimulates the release of [3H]AA from membrane phospholipids, with an EC50 of 3 microM; this effect is accompanied, with a temporal delay of approximately 4 min, by the stimulation of [3H]2DG uptake, for which the EC50 of NE is 1 microM. Since the cerebral cortex, the brain region from which astrocytes used in this study were prepared, receives a massive noradrenergic innervation, originating from the locus coeruleus, the effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects.

Serotonin-mediated acute insulin resistance in the perfused rat hindlimb but not in incubated muscle: A role for the vascular system

We have recently shown that the vasoconstrictor serotonin (5-HT) inhibits oxygen uptake in perfused hindlimb possibly due to vascular shunting. Thus in the present study the effect of 5-HT on insulin-mediated glucose uptake was assessed. Rat hindlimbs were perfused at constant flow with medium containing 8.3 mM glucose and a tracer amount of 2-deoxy-D-[1- 3H]glucose (2DG) with and without 10 μM 5-HT, 15 nM insulin and a combination of the two. 5-HT inhibited insulin-mediated stimulation of glucose uptake by 30.4% when added after insulin and 34.4% when added before insulin. In addition, 5-HT inhibited insulin-mediated 2DG uptake by perfused muscles with inhibition ranging from 32% (soleus) to 80% (extensor digitorum longus). The effects of 5-HT on insulin-mediated glucose uptake were partially reversed by vasodilation with carbachol. In contrast to the results for the hindlimb, 10 μM 5-HT had no significant effect on either basal glucose uptake or the stimulation of glucose uptake mediated by 15 nM insulin by isolated incubated soleus or extensor digitorum longus muscles. It is concluded that 5-HT impairs insulin-mediated glucose uptake in the perfused rat hindlimb that may derive from vascular shunting not apparent when muscles are incubated with 5-HT in vitro. These findings may have implications for the link between hypertension and diabetes.

Intraocular injection of APB decreases the metabolic response of the rat superior colliculus

The functional activity of the superior colliculus (SC) following flash stimulation was examined by means of 2-deoxyglucose (2DG) method in monocularly enucleated Long-Evans rats intraocularly injected with a solution of 2-amino-4-phosphonobutyric acid (APB), able to silence the ON retinal activity. After APB injection SC layers recipient of retinal axons suffered a sustained 2DG decrease as compared to controls. Moreover, whereas glucose utilization in normal rat SC appears unevenly distributed and closely related to retinal axon density, by contrast, APB-treated rats showed a rather uniform metabolic activity throughout the SC surface. Furthermore, we calculated the 2DG uptake percentage reduction in 12 SC loci of APB rats in respect to homologous loci of controls: glucose utilization decreases at the loci largely differ from each other, showing that retinal axons carrying ON activity are dispersed over the SC in a mosaic pattern. Thus, the SC metabolic map should be representative of its retinotopic organization which, in turn, depends on the asymmetric distribution in the rat's retina of W-like as well as of other ganglion cell types.

Glucose attenuation of scopolamine- and age-induced deficits in spontaneous alternation behavior and regional brain [3H]2-deoxyglucose uptake in mice

Glucose injections attenuate deficits in memory under several conditions in both rodents and humans. The present study examined effects of glucose on memory in two such amnesic populations, scopolamine-treated and old mice, and then assessed effects of glucose on brain [3H]2-deoxyglucose (2DG) uptake. In Experiment 1A, scopolamine (3 mg/kg, i.p.) significantly impaired performance of mice tested in a spontaneous alternation task. Glucose (100 mg/kg, i.p.) administration did not itself affect alternation performance, but when administered with scopolamine, it attenuated the deficit in alternation performance. Scopolamine (3 mg/kg) also resulted in significant reductions in brain 2DG uptake in hippocampus and in thalamus (Experiment 1B). Glucose (100 mg/kg) injections did not themselves affect 2DG uptake, but when administered with scopolamine, they attenuated the scopolamine-induced reductions in 2DG uptake, with the largest reversal occurring in hippocampus. Glucose similarly enhanced spontaneous alternation behavior (Experiment 2A) and hippocampal 2DG uptake (Experiment 2B) in 2-year-old mice. These findings provide additional evidence that the brain becomes more sensitive to circulating glucose in several amnestic conditions and, more generally, extend the view that circulating levels of glucose influence a wide range of brain activities.

An in vitro circadian rhythm of protein synthesis in the rat suprachiasmatic nucleus under tissue culture conditions

Because inhibitors of protein synthesis produce changes in the circadian rhythm of wheel-running activity in rodents, we examined the circadian changes of in vitro protein synthesis by the rat suprachiasmatic nucleus (SCN). We demonstrated a robust circadian rhythm of [ 14C]leucine incorporation as well as [ 3H]2-deoxyglucose (2DG) uptake by the SCN. The peak time of 2DG uptake was around circadian time 6–9 h (CT6-CT9). In contrast to 2DG uptake, the maximum rate of leucine incorporation occurred around CT22-CT0. Thus, the leucine incorporation rate preceded 2DG uptake by 6–9 h. Leucine incorporation was inhibited by protein synthesis inhibitors, but not by tetrodotoxin. Since a robust circadian rhythm of leucine incorporation by the SCN was detected in vitro by using our method, this procedure may be useful to study the circadian clock function of the SCN.

Excitatory effect of [formula omitted] and kainate receptor on the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro

The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. The previous findings indicate that excitatory amino acid (EAA) receptors play an important role in the transmission of light information from the retina to the circadian clocks. The 2-deoxyglucose (2DG) uptake shows a robust circadian change: high uptake during subjective day and low uptake during subjective night. To determine whether EAA agonists regulate 2DG uptake in the SCN, we have measured 2DG uptake in the rat SCN in vitro. We report that, during the subjective night, glutamate, N- methyl- d-aspartate (NMDA) and kainic acid (KA) cause an increase in 2DG uptake and that NMDA- or KA-induced increase of 2DG uptake is blocked by co-treatments with competitive and non-competitive NMDA or KA receptor antagonists. EAA receptor agonist-induced increase in 2DG uptake occurs only during subjective night, at circadian times when photic phase shifting of activity occurs. Taken together, those data suggest that EAA may be an important transmitter of light information from retina to the SCN.

Muscimol suppresses rCGU increase in the substantia nigra after destruction of the caudate nucleus.

Injection of ibotenic acid into the caudate nucleus caused an increase in the uptake of 2-deoxyglucose (2DG) in the ipsilateral substantia nigra pars reticulata (SNr). Increased 2DG uptake was completely suppressed by chronic infusion of muscimol, the gamma-aminobutyric acid (GABA) agonist. While delayed shorter infusion of muscimol from the 3rd to the 7th day, when 2DG accumulation was the most prominent, partially prevented this increase. These data suggest that GABA-mediated transneuronal processes play an important role in the delayed elevation in 2DG uptake in SNR but hyperexcitation due to disinhibition by the loss of GABAergic inputs may play only a partial role in this increase.

In vivo and in vitro effects of cyclosporin A on glucose transport by soleus muscles of mice

The effect of cyclosporin A (CyA) on 2-deoxyglucose (2DG) uptake by soleus muscles of ICR mice was studied in vivo and in vitro. The basal and insulin-stimulated uptakes of 2DG by the muscles as well as the plasma insulin level were significantly decreased by the in vivo treatment of mice with 20 mg/kg/day of CyA for 6 weeks (P < 0.01 and P < 0.05), whereas the insulin binding was increased inversely in the muscles from 20 mg/kg/day CyA-treated mice. The insulin-stimulated uptake of 2DG by the muscles was significantly decreased by the in vitro treatment of the muscles with 1, 10 and 100 μg/mL of CyA (P < 0.05 and P < 0.01, respectively), while the basal uptake of 2DG was not changed by the in vitro treatment of the muscles with CyA. The insulin binding to the muscles was not altered by the in vitro treatment of the muscles with CyA. These findings suggest that CyA affects not only the insulin secretion from the pancreatic islets but also the postbinding mechanisms of insulin action on the glucose transport by the muscles, which may account for a part of the diabetogenic effect of CyA.

Muscle insulin resistance may not be a primary etiological factor in the genetically obese fa/fa rat.

It is not known whether hyperinsulinemia of the genetically obese fa/fa rat occurs before insulin resistance and abnormal glucose handling or vice versa. Therefore, it was decided to study, as a function of age, the evolution of the insulin-stimulated glucose uptake measuring the in vitro uptake of its analog, 2-deoxy-D-glucose (2DG), by diaphragm. The expression of the insulin-sensitive glucose transporter (GLUT 4) mRNA and protein were also investigated in muscles. The maximum increase over baseline in 2DG uptake in response to increasing insulin concentrations in the medium was upward shifted in diaphragm from preweaned 21-day-old preobese rats relative to that in lean controls (increased responsiveness). By 31 days of age the maximum increase over baseline diaphragm 2DG uptake in response to insulin was similar in young lean and obese rats. At 70 days of age, the 2DG uptake muscle dose response to insulin was significantly downward shifted, i.e. clearly insulin resistant (decreased responsiveness). Muscle (diaphragm and extensor digitorum longus) expression of GLUT 4 mRNA and protein revealed no intergroup difference at any of the ages studied. Hyperinsulinemia was moderate in preobese animals and progressively increased with the duration of the obesity syndrome. Based on the observation that diaphragm glucose uptake of 21-day-old preobese rats was overresponsive to insulin, normoinsulin responsive at 31 days, and insulin resistant at a later time, it is concluded that muscle insulin resistance is not a primary etiological defect, but must be secondary to other pathological alterations, the nature of which remains to be elucidated.

Protective Effect of Minaprine against the Abnormal Changes of 2-Deoxyglucose Uptake by Rat Hippocampal Slices Induced by Hypoxia/Hypoglycemia

Effect of minaprine on hypoxia- or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.

Development of cat somatosensory cortex: structural and metabolic considerations.

Although research is beginning to clarify the relationship between structure and functional activity in the adult cerebral cortex, little is known about cortical development in the somatosensory cortex of cats. A number of parameters were used in this study to identify functional and anatomical correlates in the developing somatosensory cortex of kittens ranging in age from 3 to 33 d: 2-deoxyglucose (2DG) uptake, cytochrome oxidase (CO) activity, Nissl staining, and AChE activity. All of these parameters were found to reflect an immaturity that evolved to the adult-like pattern by 4-5 weeks of age. Nissl staining revealed an immature laminar pattern at birth, in which layers I, V, and VI were distinct whereas layers II-IV were homogeneous in appearance. Numerous cells could be observed at the layer VI-white matter junction and throughout the white matter, a feature not found in adults. The laminar distribution of Nissl-stained cells gradually became mature by 4-5 weeks of age. CO staining was homogeneous throughout all layers, in contrast to the adult pattern, which displays laminar differentiation. In young animals, many darkly stained CO+ cells were found at the layer VI-white matter border and in the white matter, a distribution not found in the adult. AChE staining in kittens was also distinctly different from that in adults. At birth, AChE+ fibers could be found in layers I, V, and VI but were scarce in layers II-IV. In the adult, a dense network of AChE+ fibers can be found in all layers. 2DG uptake was also immature, as little stimulus-evoked activity could be observed in animals younger than 2 weeks. A dense band of metabolic activity was found in the zone between layer VI and the white matter, whether or not a somatic stimulus was delivered. These results suggest a close correlation between the developing cytoarchitecture and the emergence of a mature pattern of functional activity in the somatosensory cortex.

Neuroprotective effect of WEB 1881 FU (nebracetam) on an ischemia-induced deficit of glucose uptake in rat hippocampal and cerebral cortical slices and CA1 field potential in hippocampal slices.

Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15-20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity.

Neuroprotective Effect of WEB 1881 FU (Nebracetam) on an Ischemia-Induced Deficit of Glucose Uptake in Rat Hippocampal and Cerebral Cortical Slices and CA1 Field Potential in Hippocampal Slices

Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) upatke and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15–20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCL-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebcetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increases of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the declinc of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity.

Mechanisms underlying somatosensory cortical dynamics: II. In vitro studies.

The response of the sensorimotor cortical slice to repetitive, single-site afferent drive is mapped using both evoked potential and metabolic mapping [2-deoxyglucose (2DG)] methods. Systematic changes (increases or decreases) in the evoked potential occur during repetitive 3-5 Hz stimulation. These resemble the changes in SI neuron response observed in the in vivo studies of the preceding companion article; they occur rapidly, recover within 1 min and are reproducible if stimulus parameters remain unchanged. Place, timing, and intensity of repetitive stimulation influence the amplitude and form of the response alterations observed at a given cortical locus. The neuron populations that exhibit different response modifications to the same repetitive stimulus are distributed nonrandomly in the slice: neurons occupying column-shaped aggregates undergo a common response alteration (either an increase or decrease) during repetitive stimulation, with sharp boundaries separating neighboring aggregates distinguishable on the basis of their dynamic behaviors. The distribution of stimulus-evoked 2DG uptake in the slice is "columnar," the dimensions of the 2DG columns corresponding to those mapped with neurophysiological methods. Taken together, the findings support the concept that repetitive stimulation causes the intrinsic network of somatosensory cortex to modify dynamically the network's response to extrinsic excitatory drive so that the local differences in the pattern of extrinsic excitatory drive to neighboring cortical columns are enhanced.

Sites of melatonin action in the brain of the house sparrow, Passer domesticus

AbstractThe pineal gland and its hormone melatonin are important for the generation of circadian rhythms by passerine birds such as the house sparrow, Passer domesticus. The sites of melatonin action within the brain of this species were determined by employing two techniques. First, the distribution of 2[125I]iodomelatonin (IMEL) binding was determined by in vitro incubation in IMEL, autoradiography, and computer image analysis. Data from these experiments indicated reversible IMEL binding in a wide array of cerebral structures primarily associated with vision. Second, the effects of exogenous melatonin on cerebral uptake of the metabolic marker 2‐deoxy[14C]glucose (2DG) were determined. Many of the same structures that bind IMEL also exhibited decreased 2DG uptake in response to melatonin administration, whereas structures that did not bind IMEL were unaffected by the hormone. The data suggest that much of the house sparrow's visual world is modulated on a circadian basis via the circadian secretion of melatonin. These observations are discussed in the context of avian circadian organization and the role it may play in the behavioral physiology of the bird.