Studies on Neuronal-Glial Metabolism of Glutamate in Cerebellar Slices

Nicklas, William J.; Krespan, Barbara

doi:10.1007/978-1-4684-1140-9_25

Cited by 7 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies by our group [8,9,22,26,27] and others [16,28,29] have shown that the metabolism of each individual substrate may be greatly influenced by the presence of other compounds which would normally be found in the intracellular and extracellulr milieu, and that the nature of these interactions provides information about the compartmentation of substrate metabolism in brain. Competition studies have been used by our group [8,9,22,26], and others [28,29], to determine if various energy substrates are metabolized in the same or differ ent compartments in brain tissue.…”

Section: Introductionmentioning

confidence: 99%

“…With substrate compe tition studies, if there is a decrease in radioactive C 0 2 production from a l4C-labelled substrate in the presence of an added unlabelled substrate, this has been inter preted as indicating that both compounds are metabo lized in the same compartment [8,9,22,26,28,29]. Conversely, if both compounds are known to be oxidized for energy but do not affect each other's oxidative metabolism, it is interpreted as indicating that the com pounds are metabolized in separate compartments [8,9,22,26,28,29]. We utilized this approach to identify multiple compartments of energy metabolism in cortical synaptic terminals.…”

Section: Introductionmentioning

confidence: 99%

“…Competition studies have been used by our group [8,9,22,26], and others [28,29], to determine if various energy substrates are metabolized in the same or differ ent compartments in brain tissue. With substrate compe tition studies, if there is a decrease in radioactive C 0 2 production from a l4C-labelled substrate in the presence of an added unlabelled substrate, this has been inter preted as indicating that both compounds are metabo lized in the same compartment [8,9,22,26,28,29]. Conversely, if both compounds are known to be oxidized for energy but do not affect each other's oxidative metabolism, it is interpreted as indicating that the com pounds are metabolized in separate compartments [8,9,22,26,28,29].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Energy Metabolism in Cortical Synaptic Terminals from Weanling and Mature Rat Brain: Evidence for Multiple Compartments of Tricarboxylic Acid Cycle Activity

McKenna¹,

Tildón²,

Stevenson³

et al. 1994

Dev Neurosci

View full text Add to dashboard Cite

It is well documented that the brain preferentially utilizes alternative substrates for energy during brain development; however, less is known about the use of these substrates by synaptic terminals. The present study compared the rates of ¹⁴CO₂ production from 1 mM D-[6-¹⁴C]glucose, L-[U-¹⁴C]glutamine, D-3-hydroxy[3-¹⁴C]butyrate, L-[U-¹⁴C]lactate and L-[U-¹⁴C]malate by synaptic terminals isolated from 17- to 18-day-old and 7- to 8-week-old rat brain. The rates of ¹⁴CO₂ production from glucose, glutamine, 3-hydroxybutyrate, lactate and malate were 8.55 ± 0.78, 25.90 ± 4.58, 42.28 ± 3.54, 48.42 ± 2.09, and 9.31 ± 1.61 nmol/h/mg protein (mean ± SEM), respectively, in synaptic terminals isolated from 17- to 18-day-old rat brain and 12.95 ± 1.64, 30.62 ± 4.19, 16.09 ± 2.62,40.33 ± 6.77, and 8.25 ± 1.69 nmol/ h/mg protein (mean ± SEM), respectively, in synaptic terminals isolated from 7- to 8-week-old rat brain. In competition studies using unlabelled added substrates, the addition of 3-hydroxybutyrate, lactate or glutamine greatly decreased the rate of ¹⁴CO₂ production from labelled glucose. Added unlabelled glucose increased the rate of ¹⁴CO₂ production from 3-hydroxybutyrate in synaptic terminals from 7- to 8-week-old rat brain, but had no effect on ¹⁴CO₂ production from any other substrates. Lactate also increased ¹⁴CO₂production from 3-hydroxybutyrate at 7–8 weeks, whereas the addition of 3-hydroxybutyrate decreased ¹⁴CO₂ production from lactate only in synaptic terminals from 17- to 18-day-old rat brain. None of the added substrates altered the rate of ¹⁴CO₂ production from labelled glutamine or malate suggesting that these substrates are metabolized in relatively distinct compartments within synaptic terminals. Overall the data demonstrate that synaptic terminals from both weanling and adult rat brain can utilize a variety of substrates for energy. In addition, the competition studies demonstrate that the interactions of substrates change with age and suggest that there are multiple compartments of energy metabolism (or tricarboxylic acid cycle activity) in isolated synaptic terminals.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Energy Metabolism in Cortical Synaptic Terminals from Weanling and Mature Rat Brain: Evidence for Multiple Compartments of Tricarboxylic Acid Cycle Activity

McKenna¹,

Tildón²,

Stevenson³

et al. 1994

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…There is considerable evidence that astrocytes also synthesize and release a number of metabolites that could be utilized by neurons for energy or neurotransmitter biosynthesis [9,[15][16][17][18][19][20][21][22][42][43][44][45], A number of studies provide information about the metabolic fate of glucose in astrocytes which is relevant to this concept. Roeder et al [12] have shown that astrocytes have a high rate of glucose uptake (4.86 nmol/min/mg protein), however, Hertz et al [41] have demonstrated that only a fraction of the labelled glucose utilized by cultured astrocytes is oxidized to C 0 2.…”

Section: Production O F Substrates By Astrocytes Fo R Metabolic Traffmentioning

confidence: 99%

“…Our group [2,5,[9][10][11][12][13] and others [14][15][16][17][18] have shown that the metabolism of energy substrates by different types of brain cells is highly regu lated and controlled in part by the localization and activi ties of specific enzymes, the transport characteristics of individual types of brain cells, and the concentration of other metabolites and effectors in the intracellular and extracellular milieu. Over the past decade it has become increasingly evident that metabolic trafficking between astrocytes and neurons or synaptic terminals also has a key role in energy metabolism in brain [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Energy Metabolism in Synaptic Terminals and Cultured Rat Brain Astrocytes: Differences Revealed Using Aminooxyacetate

et al. 1993

View full text Add to dashboard Cite

Several recent studies have demonstrated that the metabolism of energy substrates takes place in multiple compartments in both astrocytes and synaptic terminals from brain. There are a number of differences in the metabolism of astrocytes and synaptic terminals primarily due to the localization of key enzymes such as pyruvate carboxylase and glutamine synthetase in astrocytes. The present study determined the rates of ¹⁴CO₂ production from several energy substrates by primary cultures of astrocytes and cortical synaptic terminals from rat brain. The rates of ¹⁴CO₂ production from labelled substrates by astrocytes were 0.96 ± 0.13, 11.13 ± 0.67, 10.51 ± 0.35, 24.92 ± 1.66 and 4.80 ± 0.50 for D-[6-¹⁴C]gIucose, L-[U-¹⁴C]lactate, D-3-hydroxy[3-¹⁴C]butyrate, L-[U-¹⁴C]gIutamine and L-[U-¹⁴C]ma-late, respectively. The rates of ¹⁴CO₂ production were also measured in the presence of 5 mM aminooxyacetate (AOAA) to determine the effect of inhibiting the malate-aspartate shuttle and other transaminase reactions on the oxidation of energy substrates. In astrocytes the addition of AOAA decreased the rate of glutamine oxidation 5-fold, consistent with other studies showing that glutamine enters the TCA cycle via transamination. AOAA increased the rate of ¹⁴CO₂ production from labelled glucose 4-fold, suggesting that inhibition of alanine biosynthesis profoundly alters the utilization of glucose by astrocytes. AOAA also increased the oxidation of lactate and 3-hydroxybutyrate 36 and 58%, respectively. The rates of ¹⁴CO₂ production from labelled substrates by synaptic terminals were 13.12 ± 1.05, 35.29 ± 3.58, 17.66 ± 1.95, 30.18 ± 1.10 and 9.95 ± 1.29, respectively, for glucose, lactate, 3-hydroxybutyrate, glutamine and malate, demonstrating that all substrates were oxidized at a higher rate by synaptic terminals than by astrocytes. The addition of AOAA decreased the rate of ¹⁴CO₂ production from labelled lactate by 57% suggesting that the use of lactate for energy in synaptic terminals is tightly coupled to the activity of the malate-aspartate shuttle. AOAA had no effect on the rate of ¹⁴CO₂ production from labelled glutamine, demonstrating that exogenous glutamine enters the TCA cycle in synaptic terminals via glutamate dehydrogenase, not via transamination as is the case with astrocytes. AOAA had no significant effect on the rates of oxidation of glucose, 3-hydroxybutyrate-and malate by synaptic terminals. These findings demonstrate that inhibiting transamination with AOAA had very different effects on the oxidation of energy substrates in the two preparations, suggesting that the regulation of metabolism is quite different in astrocytes and synaptic terminals. These studies also underscore the importance of utilizing multiple energy substrates since the presence of AOAA altered energy metabolism in some, but not all, co...

show abstract

Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy

Sorbi

Tonini

Giannini

et al. 1986

Annals of Neurology

View full text Add to dashboard Cite

Glutamate dehydrogenase (GDH) activity and its allosteric modulation by purine nucleotides were studied in platelet preparations from 4 patients with a nondominant form of adult-onset olivopontocerebellar atrophy (OPCA) and in affected and nonaffected members of two families with a dominant form of OPCA. A partial deficiency of GDH activity (40 to 50% of control values) was present in 3 patients with nondominant OPCA and in 2 patients, father and son, with a dominant form of OPCA. Platelet GDH from these patients and controls was regularly inactivated by 2 mM guanosine-5'-triphosphate (GTP) and simulated one- to twofold by 2 mM adenosine-5'-diphosphate (ADP). In the presence of 0.2% Triton X-100, the activating effect of ADP was enhanced four- to sixfold. The partial deficiency in maximum catalytic activity observed in these patients persisted under all conditions used for enzyme assay. In affected members, but not in one unaffected member of another family with a dominant type of OPCA, GDH activity was in the control range but was not activated by ADP in either the presence or absence of Triton. These results suggest that there may be at least two possible alterations of GDH in patients with OPCA: one which decreases the maximum catalytic activity and one which impairs the regulatory properties of the enzyme. Furthermore, this study suggests that platelet GDH determination in patients with OPCA may provide a simple and useful tool to classify these disorders and to understand the basic pathophysiological mechanisms involved.

show abstract

Studies on Neuronal-Glial Metabolism of Glutamate in Cerebellar Slices

Cited by 7 publications

References 22 publications

Energy Metabolism in Cortical Synaptic Terminals from Weanling and Mature Rat Brain: Evidence for Multiple Compartments of Tricarboxylic Acid Cycle Activity

Energy Metabolism in Cortical Synaptic Terminals from Weanling and Mature Rat Brain: Evidence for Multiple Compartments of Tricarboxylic Acid Cycle Activity

Regulation of Energy Metabolism in Synaptic Terminals and Cultured Rat Brain Astrocytes: Differences Revealed Using Aminooxyacetate

Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy

Contact Info

Product

Resources

About