Metabolite Exchanges and Signal Trafficking Between Glial Cells and Neurons in the Insect Retina

Tsacopoulos, M.; Poitry, Serge

doi:10.1007/978-1-59259-468-9_4

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…Ammonia essentially is produced in the mitochondria of photoreceptors ( Fig. 1, left) and subsequently is released into the extracellular space (Tsacopoulos and Poitry, 1995;Coles et al, 1996a;Tsacopoulos et al, 1997). Previously, we showed that light stimulation of honeybee retinal slices or exposure to dinitrophenol (both induce an increase in the O 2 consumption of photoreceptors; Tsacopoulos et al, 1987) causes an increased release of NH 4 ϩ into the extracellular space.…”

Section: Ammonia Transport and Signalingmentioning

confidence: 88%

Ammonium and Glutamate Released by Neurons Are Signals Regulating the Nutritive Function of a Glial Cell

1997

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Glial cells transform glucose to a fuel substrate taken up and used by neurons. In the honeybee retina, photoreceptor neurons consume both alanine supplied by glial cells and exogenous proline. Ammonium (NH4+) and glutamate, produced and released in a stimulus-dependent manner by photoreceptor neurons, contribute to the biosynthesis of alanine in glia. Here we report that NH4+ and glutamate are transported into glia and that a transient rise in the intraglial concentration of NH4+ or of glutamate causes a net increase in the level of reduced nicotinamide adenine dinucleotides [NAD(P)H]. Biochemical measurements indicate that this is attributable to activation of glycolysis in glial cells by the direct action of NH4+ and glutamate on at least two enzymatic reactions: those catalyzed by phosphofructokinase (PFK; ATP:D-fructose-6-phosphotransferase, EC2.7.1.11) and glutamate dehydrogenase (GDH; L-glutamate:NAD oxidoreductase, deaminating; EC1.4.1.3). This activation leads to an increase in the production and release of alanine by glia. This signaling, which depends on the rate of conversion of NH4+ and glutamate to alanine and alpha-ketoglutarate, respectively, in the glial cells, raises the novel possibility of a tight regulation of the nutritive function of glia.

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Section: Ammonia Transport and Signalingmentioning

confidence: 88%

Ammonium and Glutamate Released by Neurons Are Signals Regulating the Nutritive Function of a Glial Cell

1997

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“…Studies of glycogen and glucose metabolism in mammalian astrocytes in culture and of the honeybee retinal glial cells as well as other brain cell preparations have clearly demonstrated that these cells can mobilize metabolic equivalents from glycogen or glucose (Dringen et al, 1993b;Tsacopoulos, 1995;Tsacopoulos and Magistretti, 1996;Tsacopoulos et al, 1988Tsacopoulos et al, , 1994). It appears that glycogen and glucose are primarily converted to lactate or alanine, which are secreted from the cells and which may subsequently be utilized in neurons as energy substrates.…”

Section: Glucose and Lactate Metabolismmentioning

confidence: 99%

Trafficking between glia and neurons of TCA cycle intermediates and related metabolites

Schousboe¹,

Westergaard

Waagepetersen³

et al. 1997

Glia

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Net synthesis of the neurotransmitter amino acids glutamate and GABA can take place either from glutamine or from alpha-ketoglutarate or another tricarboxylic acid (TCA) cycle intermediate plus an amino acid as donor of the amino group. Since neurons lack the enzymes glutamine synthetase and pyruvate carboxylase that are expressed only in astrocytes, trafficking of these metabolites must take place between neurons and astrocytes. Moreover, it is likely that astrocytes play an important role in maintaining the energy status in neurons supplying energy substrates, e.g., in the form of lactate. The role of trafficking of glutamine, TCA cycle constituents as well as the role of lactate as an energy source in neurons is discussed. Using [U-13C] lactate and NMR spectroscopy, it is shown that lactate that can be produced in astrocytes can be taken up into neurons and metabolized through the TCA-cycle leading to labeling of TCA cycle intermediates plus amino acids derived from these. The labeling pattern of glutamate and GABA indicates that C atoms from lactate remain in the cycle for several turns and that GABA formation may involve more than one glutamate pool, i.e., that compartmentation may exist. Additionally, a possible role of citrate as a chelator of Zn++ with regard to neuronal excitation is discussed. Astrocytes produce large quantities of citrate which by chelation of Zn++ alters the excitable state of neurons via regulation of N-methyl-D-aspartate receptor activity. Thus, astrocytes may regulate neuronal activity at a number of different levels.

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“…Ammonia brain levels correlate well with neuronal activity: a reduction in functional activity is associated with decreased ammonia levels, while elevated ammonia levels are observed with intense neuronal activity (Benjamin, 1982). Provocative data by Tsacopoulos (1995) suggest that ammonia released during neuronal activation serves as a signal to stimulate glial glycolysis (via activation of phosphofructokinase) (Lowry and Passonneau, 1966). This generates glutamate for the synthesis of alanine, which is released by glia and taken up by neurons for fuel (after conversion to pyruvate or glutamate).…”

Section: Ammonia Metabolism and Neurotoxicitymentioning

confidence: 99%

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Norenberg

Huo

Neary

et al. 1997

Glia

135

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Abnormalities in glutamate metabolism and glutamatergic neurotransmission appear to play a major role in the pathogenesis of hyperammonemia and hepatic encephalopathy. Astrocytes may be involved in these derangements as ammonia has been shown to impair the ability of these cells to take up glutamate. This study presents a northern blot analysis of the GLT-1 glutamate transporter in hyperammonemic rats, and in rats with thioacetamide-induced acute liver failure. Our findings demonstrate a downregulation of GLT-1 mRNA in both conditions. This article examines the potential impact of deficits in glutamate uptake on energy metabolism and glutamatergic neurotransmission in the context of abnormalities in glial-neuronal interactions. We propose that an ammonia-induced abnormality in astroglial glutamate uptake constitutes a critical aspect in the pathogenesis of hepatic encephalopathy and other hyperammonemic conditions.

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Metabolite Exchanges and Signal Trafficking Between Glial Cells and Neurons in the Insect Retina

Cited by 4 publications

References 45 publications

Ammonium and Glutamate Released by Neurons Are Signals Regulating the Nutritive Function of a Glial Cell

Ammonium and Glutamate Released by Neurons Are Signals Regulating the Nutritive Function of a Glial Cell

Trafficking between glia and neurons of TCA cycle intermediates and related metabolites

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

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