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Leif Hertz

Publications and source records attributed to Leif Hertz.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens.

Glycolysis and glycogenolysis are involved in memory processing in day-old chickens and, aside from the provision of energy for neuronal and astrocytic energy metabolism these pathways enable astrocytes to supply neurones with precursor for transmitter glutamate by glucose-based de novo synthesis. We have previously shown that memory processing for bead discrimination learning is dependent on glycolysis; however, the metabolic inhibitor used, iodoacetate, inhibits pyruvate formation from both glucose and glycogen. At specific time points after training transient reductions in brain glycogen content occur, mirrored by increases in glutamate/glutamine content. In the present study, we used intracerebral injection of a glycogen phosphorylase inhibitor, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), which does not affect glucose breakdown, to evaluate the role of glycogen metabolism in memory consolidation. Dose-dependent inhibition of learning occurred when DAB was administered at specific time periods in relation to training: (i) 5 min before training, (ii) around 30 min posttraining, and (iii) 55 min posttraining. After injection at either of the two earlier periods, memory disappeared after consolidation 30 min postlearning, and after injection 55 min after learning memory was absent at 70 min. The memory loss caused by early administration could be prevented after training by central injection of the glutamate precursor glutamine or the astrocyte-specific substrate acetate together with aspartate, substituting for pyruvate carboxylation. Thus, glycogenolysis is essential for learning in this paradigm and, aside from energy supply considerations, we suggest that an important role for glycogenolysis is to provide neurones with glutamine as the precursor for neuronal glutamate and GABA.

Animals↗
PubMed2006

Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.

Astrocytic energy demand is stimulated by K(+) and glutamate uptake, signaling processes, responses to neurotransmitters, Ca(2+) fluxes, and filopodial motility. Astrocytes derive energy from glycolytic and oxidative pathways, but respiration, with its high-energy yield, provides most adenosine 5' triphosphate (ATP). The proportion of cortical oxidative metabolism attributed to astrocytes ( approximately 30%) in in vivo nuclear magnetic resonance (NMR) spectroscopic and autoradiographic studies corresponds to their volume fraction, indicating similar oxidation rates in astrocytes and neurons. Astrocyte-selective expression of pyruvate carboxylase (PC) enables synthesis of glutamate from glucose, accounting for two-thirds of astrocytic glucose degradation via combined pyruvate carboxylation and dehydrogenation. Together, glutamate synthesis and oxidation, including neurotransmitter turnover, generate almost as much energy as direct glucose oxidation. Glycolysis and glycogenolysis are essential for astrocytic responses to increasing energy demand because astrocytic filopodial and lamellipodial extensions, which account for 80% of their surface area, are too narrow to accommodate mitochondria; these processes depend on glycolysis, glycogenolysis, and probably diffusion of ATP and phosphocreatine formed via mitochondrial metabolism to satisfy their energy demands. High glycogen turnover in astrocytic processes may stimulate glucose demand and lactate production because less ATP is generated when glucose is metabolized via glycogen, thereby contributing to the decreased oxygen to glucose utilization ratio during brain activation. Generated lactate can spread from activated astrocytes via low-affinity monocarboxylate transporters and gap junctions, but its subsequent fate is unknown. Astrocytic metabolic compartmentation arises from their complex ultrastructure; astrocytes have high oxidative rates plus dependence on glycolysis and glycogenolysis, and their energetics is underestimated if based solely on glutamate cycling.

Animals↗
PubMed2006

Glutamate, a neurotransmitter--and so much more. A synopsis of Wierzba III.

It appears almost incredible that the first indications that glutamate excites brain tissue were obtained during the second half of the 20th century, that vesicles containing glutamate were demonstrated in glutamatergic neurons less than 25 years ago, and that glutamate was not accepted as the major excitatory transmitter until about the same time. During this span of time it has also become realized that glutamate is so much more than a conventional neurotransmitter: (1) astrocytes express vesicles accumulating glutamate by vesicular transporters akin to the vesicular glutamate transporters in glutamatergic neurons, and they release glutamate by exocytosis; (2) a series of metabolic processes in astrocytes (glutamate uptake, glutamine synthetase activity, glutamine release) are involved in neuronal reutilization of transmitter glutamate; (3) glutamine may also be utilized for synthesis of GABA, the major inhibitory transmitter; (4) de novo synthesis of glutamate accounts for 20% of cerebral glucose metabolism, all of which initially occurs in astrocytes, and at steady state a corresponding amount of glutamate is oxidatively degraded, mainly or exclusively in astrocytes; (5) tissue contents of glutamate/glutamine increase during enhanced glutamatergic activity, i.e., astrocytic de novo synthesis exceeds astrocytic metabolic degradation of glutamate.

Amino Acid Transport System X-AG↗
PubMed2005

Importance of glutamate-generating metabolic pathways for memory consolidation in chicks.

Glutamatergic and noradrenergic stimulation is essential for formation of memory of single-trial discriminative avoidance of colored beads in the 1-day-old chick. Transmitter glutamate is released soon after training and again before memory consolidation 30 min after training. Memory consolidation is abolished by posttraining injection of iodoacetate, which inhibits glycolysis and thus not only energy metabolism but also pyruvate carboxylase-dependent glucose conversion to glutamate, needed for consolidation; a similar effect is evoked by the antagonists propranolol acting at beta(2)-adrenoceptors or SR59230A acting at beta(3)-adrenoceptors. This paper shows that the effect of these inhibitors can be overcome by central injection of glutamine, providing an alternate source of transmitter glutamate and compensating for the inhibition of glycolysis by iodoacetate or the blockade of adrenergic stimulation of glycogenolysis by propranolol or of glucose uptake by SR59230A. Conversely, inhibition of memory consolidation by methionine sulfoximine (MSO), an inhibitor of glutamine synthetase and thus of the glutamate-glutamine cycle, essential for neuronal reaccumulation of previously released transmitter glutamate, could be challenged by noradrenaline, stimulating glucose uptake and glycogenolysis and providing glutamate synthesis from glucose to compensate for the lack of return of previously released glutamate. Also, administration of either glutamine or noradrenaline could prevent the spontaneous decay of labile memory 30 min after training on a weakened stimulus, suggesting that direct supply of glutamate from glucose may secure sufficient supplies of transmitter glutamate for release prior to memory consolidation at 30 min.

Animals↗
PubMed2005

Astrocytic contributions to bioenergetics of cerebral ischemia.

Astrocytes are multifunctional cells that interact with neurons and other astrocytes in signaling and metabolic functions, and their resistance to pathophysiological conditions can help restrict loss of tissue after an ischemic event provided adequate nutrients are supplied to support their requirements. Astrocytes have substantial oxidative capacity and mechanisms to upregulate glycolytic capability when respiration is impaired. An astrocytic enzyme that synthesizes a powerful activator of glycolysis is not present in neurons, endowing astrocytes with the ability to sustain ATP production under restrictive conditions. The monocarboxylic acid transporter (MCT) isoforms predominating in astrocytes are optimized to facilitate very large increases in lactate flux as lactate concentration increases within (1-3 mM) and above (>3 mM) the normal range. In sharp contrast, the major neuronal MCT serves as a barrier to increased transmembrane transport as lactate rises above 1 mM, restricting both entry and efflux. Lactate can serve as fuel during recovery from ischemia but direct evidence that lactate is oxidized by neurons (vs. astrocytes) to maintain synaptic function is lacking. Astrocytes have critical roles in regulation of ionic homeostasis and control of extracellular glutamate levels, and spreading depression associated with ischemia places high demands on energy supplies in astrocytes and contributes to metabolic exhaustion and demise. Disruption of Ca2+ homeostasis, generation of oxygen free radicals and nitric oxide, and mitochondrial depolarization contribute to astrocyte death during and after a metabolic insult. Novel pharmaceutical agents targeted to astrocytes and hyperoxic therapy that restores penumbral oxygen level during energy failure might improve postischemic outcome.

Animals↗
PubMed2005

Nucleoside transporter expression and function in cultured mouse astrocytes.

Uptake of purine and pyrimidine nucleosides in astrocytes is important for several reasons: (1) uptake of nucleosides contributes to nucleic acid synthesis; (2) astrocytes synthesize AMP, ADP, and ATP from adenosine and GTP from guanosine; and (3) adenosine and guanosine function as neuromodulators, whose effects are partly terminated by cellular uptake. It has previously been shown that adenosine is rapidly accumulated by active uptake in astrocytes (Hertz and Matz, Neurochem Res 14:755-760, 1989), but the ratio between active uptake and metabolism-driven uptake of adenosine is unknown, as are uptake characteristics for guanosine. The present study therefore aims at providing detailed information of nucleoside transport and transporters in primary cultures of mouse astrocytes. Reverse transcription-polymerase chain reaction identified the two equilibrative nucleoside transporters, ENT1 and ENT2, together with the concentrative nucleoside transporter CNT2, whereas CNT3 was absent, and CNT1 expression could not be investigated. Uptake studies of tritiated thymidine, formycin B, guanosine, and adenosine (3-s uptakes at 1-4 degrees C to study diffusional uptake and 1-60-min uptakes at 37 degrees C to study concentrative uptake) demonstrated a fast diffusional uptake of all four nucleosides, a small, Na(+)-independent and probably metabolism-driven uptake of thymidine (consistent with DNA synthesis), larger metabolism-driven uptakes of guanosine (consistent with synthesis of DNA, RNA, and GTP) and especially of adenosine (consistent with rapid nucleotide synthesis), and Na(+)-dependent uptakes of adenosine (consistent with its concentrative uptake) and guanosine, rendering neuromodulator uptake independent of nucleoside metabolism. Astrocytes are accordingly well suited for both intense nucleoside metabolism and metabolism-independent uptake to terminate neuromodulator effects of adenosine and guanosine.

Adenosine↗
PubMed2005

Ammonia effects on pyruvate/lactate production in astrocytes--interaction with glutamate.

Ammonia exerts a multitude of metabolic and non-metabolic effects on brain tissue. In the present communication we have investigated its effect on lactate production rates, pyruvate production rates and pyruvate/lactate ratios in mouse cerebrocortical astrocytes and neurons in primary cultures. No effects were found in neurons. All three parameters were affected by ammonia in astrocytes, but less potently and to a smaller degree in cells that had been treated with dibutyryl cyclic AMP (morphologically differentiated cells) than in untreated cells (morphologically undifferentiated cells). In the differentiated cells ammonia had virtually no effect up to a concentration of 1.0 mM, but at 3.0 mM it increased lactate production and decreased pyruvate/lactate ratio significantly. In the undifferentiated cells ammonia greatly increased lactate accumulation (by 80% at 3.0 mM) and it inhibited pyruvate accumulation (by 40% at 3.0 mM). It thereby reduced the pyruvate/lactate ratio progressively within the entire range 0.1-3.0 mM ammonia. In support of the hypothesis that the ammonia-induced reduction of pyruvate/lactate ratio is secondary to depletion of cellular glutamate by formation of glutamine (and glutathione) and a resulting interruption of the malate-aspartate shuttle (MAS), the addition of glutamate to the incubation medium significantly diminished the ammonia-induced reduction of pyruvate/lactate ratio, whereas it had no effect on the increased lactate production. It is discussed that MAS interruption may have additional consequences in astrocytes.

Ammonia↗
PubMed2004

Astrocytic control of glutamatergic activity: astrocytes as stars of the show.

It is a major recent finding that astrocytes can influence synaptic activity by release of glutamate, but many other glutamate-mediated activities are also controlled by astrocytes. Even the most obvious neuronal function of glutamate - its release as a transmitter - is regulated by astrocytes; these cells are needed for formation of precursors for glutamate synthesis, for reuptake of released transmitter, and for disposal of excess glutamate. Without astrocytic involvement, normal function of glutamatergic neurons is not possible, as exemplified by almost instantaneous abrogation of normal vision and learning upon inhibition of astrocyte-specific metabolic pathways. In addition, astrocytes are essential for production of the neuroprotectant glutathione, yet they can also contribute to neuronal death during ischemia by maintaining glutamine synthesis, enabling neuronal formation of neurotoxic glutamate.

Animals↗
PubMed2003

Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick.

Passive avoidance learning is with advantage studied in day-old chicks trained to distinguish between beads of two different colors, of which one at training was associated with aversive taste. During the first 30-min post-training, two periods of glutamate release occur in the forebrain. One period is immediately after the aversive experience, when glutamate release is confined to the left hemisphere. A second release, 30 min later, may be bilateral, perhaps with preponderance of the right hemisphere. The present study showed increased pool sizes of glutamate and glutamine, specifically in the left hemisphere, at the time when the first glutamate release occurs, indicating de novo synthesis of glutamate/glutamine from glucose or glycogen, which are the only possible substrates. Behavioral evidence that memory is extinguished by intracranial administration at this time of iodoacetate, an inhibitor of glycolysis and glycogenolysis, and that the extinction of memory is counteracted by injection of glutamine, supports this concept. A decrease in forebrain glycogen of similar magnitude and coinciding with the increase in glutamate and glutamine suggests that glycogen rather than glucose is the main source of newly synthesized glutamate/glutamine. The second activation of glutamatergic activity 30 min after training, when memory is consolidated into stable, long-term memory, is associated with a bilateral increase in pool size of glutamate/glutamine. No glycogenolysis was observed at this time, but again there is a temporal correlation with sensitivity to inhibition by iodoacetate and rescue by glutamine, indicating the importance of de novo synthesis of glutamate/glutamine from glucose or glycogen.

Analysis of Variance↗
PubMed2003

Alpha-adrenergic stimulation of ERK phosphorylation in astrocytes is alpha(2)-specific and may be mediated by transactivation.

The highly specific alpha(2)-adrenergic agonist, dexmedetomidine, has hypnotic-sedative, anesthetic-sparing and analgesic effects, and it protects neurons against ischemia. The alpha(1)-adrenergic agonist, phenylephrine, does not share dexmedetomidine's pharmacological properties, although both dexmedetomidine and phenylephrine increase free cytosolic Ca(2+) ([Ca(2+)](i)) in astrocytes, and most of dexmedetomidine's actions in the brain are exerted on postjunctional receptors. alpha(2)-Adrenergic receptors are abundant on astrocytes. Dexmedetomidine-mediated 'down-streamn' signal transduction was therefore investigated in primary cultures of mouse astrocytes and contrasted with that of phenylephrine. The cultures were incubated with dexmedetomidine concentrations known to be pharmacologically active and to act specifically on alpha(2)-adrenergic receptors (25-100 nM). ERK(1/2) phosphorylation was measured using specific antibodies. Peak increases of ERK(1/2) phosphorylation occurred at 50 nM dexmedetomidine, with less effect at higher concentrations. Phenylephrine caused ERK phosphorylation only at a concentration high enough to exert non subtype-specific effects (10 microM), and this effect was counteracted by the alpha(2)-adrenergic antagonist atipamezole. The phosphorylation of ERK was reduced by tyrphostin AG1478, an inhibitor of phosphorylation of the epidermal growth factor receptor (EGFR), and by heparin, which neutralizes heparin-binding epithelial growth factor (HB-EGF), suggesting the involvement of a transactivation process, in which alpha(2)-adrenergic stimulation leads to proteolytic shedding of HB-EGF (and perhaps other EGFR agonists) from transmembrane-spanning precursors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

Astrocytic amino acid metabolism under control conditions and during oxygen and/or glucose deprivation.

Amino acid contents were measured in 1- and 3-week-old primary cultures of astrocytes and in their incubation media, an amino acid-free salt solution with or without glucose, during 3-h incubation under normoxic or anoxic conditions. Most essential amino acids were rapidly released to the medium during the beginning of the incubation. A subsequent slow medium increase reflected proteolysis. Glutamate and aspartate were absent from the media during all conditions, indicating fueling of their uptake by either glycolytically or oxidatively derived energy. The total content of glutamine increased, except during incubation in glucose-deprived media, when it declined or remained constant. Changes in aspartate were negligible, suggesting oxidative degradation of aspartate-derived oxaloacetate during normoxia and its reduction to succinate during anoxia, driving regeneration of NAD+ from NADH. An increase of alanine was reduced in glucose-free media, whereas serine showed especially large increase during isolated glucose deprivation, suggesting its production from glutamine via 3-phosphoglycerate.

Amino Acids↗
PubMed2002

Amobarbital inhibits K(+)-stimulated glucose oxidation in cerebellar granule neurons by two mechanisms.

The study aimed at determining mechanism(s) by which amobarbital (amytal) suppresses glucose oxidation in cerebellar granule neurons in primary cultures, a glutamatergic preparation. When challenged with a depolarizing K(+) concentration (55 mM), the cells doubled their rate of glucose oxidation (production of 14CO(2) from U-[14C]glucose) and glycolysis (lactate accumulation). At normal K(+) concentration, amobarbital reduced 14CO(2) production with half-maximum effect at 0.5-1 mM; at 55 mM K(+), the inhibition was more potent, with more than half of the K(+)-induced stimulation abolished at 50 microM. Dixon plot analysis showed a single inhibitory mechanism at 5.4 mM K(+), but at 55 mM K(+), two kinetically different mechanisms could be distinguished. A more pronounced compensatory amobarbital-induced increase in glycolysis at 5.4 than at 55 mM K(+) suggested that amobarbital in addition to its inhibition of mitochondrial respiration inhibited K(+)-induced increase in energy demand, probably by its known suppression of stimulated glutamate release.

Amobarbital↗
PubMed2002

Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration.

The effects were studied of short-term (1 week) versus long-term (2-3 weeks) fluoxetine treatment of primary cultures of mouse astrocytes, differentiated by treatment with dibutyryl cyclic AMP. From previous experiments it is known that acute treatment with fluoxetine stimulates glycogenolysis and increases free cytosolic Ca2+ concentration ([Ca2+]i]) in these cultures, whereas short-term (one week) treatment with 10 microM down-regulates the effects on glycogen and [Ca2+]i, when fluoxetine administration is renewed (or when serotonin is administered). Moreover, antagonist studies have shown that these responses are evoked by activation of a 5-HT2, receptor that is different from the 5-HT2A receptor and therefore at that time tentatively were interpreted as being exerted on 5-HT2C receptors. In the present study the cultures were found by RT-PCR to express mRNA for 5-HT2A and 5-HT2B receptors, but not for the 5-HT2C receptor, identifying the 5-HT2 receptor activated by fluoxetine as the 5-HT2B receptor, the most recently cloned 5-Ht2 receptor and a 5-HT receptor known to be more abundant in human, than in rodent, brain. Both short-term and long-term treatment with fluoxetine increased the specific binding of [3H]mesulergine, a ligand for alL three 5-HT2 receptors. Long-term treatment with fluoxetine caused an agonist-induced up-regulation of the glycogenolytic response to renewed administration of fluoxetine, whereas short-term treatment abolished the fluoxetine-induced hydrolysis of glycogen. Thus, during a treatment period similar to that required for fluoxetine's clinical response to occur, 5-HT2B-mediated effects are initially down-regulated and subsequently up-regulated.

Animals↗
PubMed2002

Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons.

Pyruvate recycling was studied in primary cultures of mouse cerebrocortical astrocytes, GABAergic cerebrocortical interneurons, and co-cultures consisting of both cell types by measuring production of [4-(13)C]glutamate from [3-(13)C]glutamate by aid of nuclear magnetic resonance spectroscopy. This change in the position of the label can only occur by entry of [3-(13)C]glutamate into the tricarboxylic acid (TCA) cycle, conversion of labeled alpha-ketoglutarate to malate or oxaloacetate, malic enzyme-mediated decarboxylation of malate to pyruvate or phosphoenolpyruvate carboxykinase-mediated conversion of oxaloacetate to phosphoenolpyruvate and subsequent hydrolysis of the latter to pyruvate, and introduction of the labeled pyruvate into the TCA cycle, i.e., after exit of the carbon skeleton of pyruvate from the TCA cycle followed by re-entry of the same pyruvate molecules via acetyl CoA. In agreement with earlier observations, pyruvate recycling was demonstrated in astrocytes, indicating the ability of these cells to undertake complete oxidative degradation of glutamate. The recycled [4-(13)C]glutamate was not further converted to glutamine, showing compartmentation of astrocytic metabolism. Thus, absence of recycling into glutamine in the brain in vivo cannot be taken as indication that pyruvate recycling is absent in astrocytes. No recycling could be demonstrated in the cerebrocortical neurons. This is consistent with a previously demonstrated lack of incorporation of label from glutamate into lactate, and it also indicates that mitochondrial malic enzyme is not operational. Nor was there any indication of pyruvate recycling in the co-cultures. Although this may partly be due to more rapid depletion of glutamate in the co-cultures, this observation at the very least indicates that pyruvate recycling is not up-regulated in the neuronal-astrocytic co-cultures.

Animals↗
PubMedDate not supplied

Lactate transport and transporters: general principles and functional roles in brain cells.

Lactate is transported across cell membranes by diffusional, saturable cotransport with protons, mediated by monocarboxylate transporters (MCTs). This transport is bidirectional and in the absence of a transcellular H(+) gradient, it can increase the intracellular concentration of lactate up to but not beyond the extracellular level (or vice versa). If extra- and intracellular pH differ, however, the equilibrium level is determined by the gradients of both lactate anions and protons. Rates of lactate uptake are determined most often by measuring uptake of labeled lactate, e.g., [U-14C]lactate. In the case of lactate and other compounds that are metabolized, errors are introduced easily because continuing inwardly directed diffusional net transport of label can be achieved by intracellular metabolism, reducing the intracellular level of the nonmetabolized lactate and thus maintaining a concentration gradient between extra- and intracellular concentrations of the nonmetabolized compound (metabolism-driven uptake). For measurement of facilitated diffusion kinetics, it is essential that the period during which the uptake is measured is short enough that little or no metabolism-driven uptake contributes to the measured uptake (or that first-order regression analysis is carried out to obtain initial uptake rates from nonlinear traces). To achieve initial uptake rates, incubation periods well below 1 min are generally required. Lactate uptake is fast in astrocytes, which express powerful, low-affinity MCTs, i.e., MCT1 and MCT4. Due to the low affinity of these transporters, they respond to increased lactate gradients with enhanced transporter activity. The predominant MCT in neurons is the high-affinity MCT2, which can only increase its activity to a limited extent in the face of an increased lactate gradient. This is reflected by a high-affinity lactate uptake, although most investigators also have demonstrated a component of lactate uptake with lower affinity. In both neurons and astrocytes, however, facilitated diffusion is fast enough that under most conditions lactate fluxes will be determined mainly by the rate of metabolism-driven uptake, and MCT-mediated transport only will be rate-limiting after establishment of large transmembrane gradients.

Animals↗
PubMedDate not supplied

Intercellular metabolic compartmentation in the brain: past, present and future.

The first indication of 'metabolic compartmentation' in brain was the demonstration that glutamine after intracisternal [14C]glutamate administration is formed from a compartment of the glutamate pool that comprises at most one-fifth of the total glutamate content in the brain. This pool, which was designated 'the small compartment,' is now known to be made up predominantly or exclusively of astrocytes, which accumulate glutamate avidly and express glutamine synthetase activity, whereas this enzyme is absent from neurons, which eventually were established to constitute 'the large compartment.' During the following decades, the metabolic compartment concept was refined, aided by emerging studies of energy metabolism and glutamate uptake in cellularly homogenous preparations and by the histochemical observations that the two key enzymes glutamine synthetase and pyruvate carboxylase are active in astrocytes but absent in neurons. It is, however, only during the last few years that nuclear magnetic resonance (NMR) spectroscopy, assisted by previously obtained knowledge of metabolic pathways, has allowed accurate determination in the human brain in situ of actual metabolic fluxes through the neuronal tricarboxylic acid (TCA) cycle, the glial, presumably mainly astrocytic, TCA cycle, pyruvate carboxylation, and the 'glutamate-glutamine cycle,' connecting neuronal and astrocytic metabolism. Astrocytes account for 20% of oxidative metabolism of glucose in the human brain cortex and accumulate the bulk of neuronally released transmitter glutamate, part of which is rapidly converted to glutamine and returned to neurons in the glutamate-glutamine cycle. However, one-third of released transmitter glutamate is replaced by de novo synthesis of glutamate from glucose in astrocytes, suggesting that at steady state a corresponding amount of glutamate is oxidatively degraded. Net degradation of glutamate may not always equal its net production from glucose and enhanced glutamatergic activity, occurring during different types of cerebral stimulation, including the establishment of memory, may be associated with increased de novo synthesis of glutamate. This process may contribute to a larger increase in glucose utilization rate than in rate of oxygen consumption during brain activation. The energy yield in astrocytes from glutamate formation is strongly dependent upon the fate of the generated glutamate.

Animals↗