Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes

Subbarao, Kala V.; Hertz, Leif

doi:10.1016/0006-8993(90)90028-a

Cited by 120 publications

(90 citation statements)

References 33 publications

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“…Furthermore, as shown in Fig. 5, the neuropro tective effects of both agents can be abolished by brief exposure to NE or dB cAMP , sufficient to de plete glycogen back down to near control levels by induction of rapid glycogenolysis (Opler and Mak man, 1972;Subbarao and Hertz, 1990). Exposure to NE and dBcAMP without prior treatment with in sulin or MSO caused little or no increase in neuro nal vulnerability to glucose deprivation.…”

Section: Discussionmentioning

confidence: 91%

“…The cultures were used for biochemical determinations or glucose depriva tion experiments after 24 h incubation. Some of these cultures were also exposed to 20 j-lM norepinephrine (NE) or 1 mM dibutyryl cAMP (dBcAMP), agents known to decrease glial glycogen content (Opler and Makman, 1972;Subbarao and Hertz, 1990), for 30 min immediately before use. All reagents were added from 50x or 100x stock solutions prepared in water, except insulin which was stored at 1 ,000 x (1 mM) in 0.1% albumin.…”

Section: Manipulation Of Glycogen Levelsmentioning

confidence: 99%

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Glial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro

Swanson

Choi

1993

J Cereb Blood Flow Metab

225

155

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Summary: Glia perform several energy-dependent func tions that may aid neuronal survival under pathological conditions. Glycogen is the major energy reserve in brain, and it is localized almost exclusively to astrocytes. Using murine cortical cell cultures containing both glia and neu rons, we examined the effect of altered glial glycogen stores on neuronal survival following glucose depriva tion. As previously reported, cultures exposed for several hours to media lacking glucose developed widespread neuronal degeneration without glial degeneration. If glial astrocyte glycogen content was increased to 2-3 times Astrocytes perform multiple functions essential for the normal activity of neurons in the brain. In addition to providing mechanical support and trophic factors (Bunge and Waksman, 1985), astro cytes maintain homeostasis of the brain extracellu lar fluid (ECF). Astrocytes are largely responsible for the uptake and catabolism of excitatory amino acids and other neurotransmitters (Ericinska et aI., 1986;Hertz, 1979;Varon and Somjen, 1979), and for the uptake and redistribution of K + (Hertz, 198 1; Jendelova and Sykova, 199 1). Astrocytic am monia fixation provides the only mechanism other than diffusion for clearing brain ammonia (Cooper and Lai, 1987). Astrocytes may also play an impor-

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Section: Discussionmentioning

confidence: 91%

Section: Manipulation Of Glycogen Levelsmentioning

confidence: 99%

Glial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro

Swanson

Choi

1993

J Cereb Blood Flow Metab

225

155

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“…As noradrenaline promotes glycogenolysis (Magistretti, 1988;Subbarao and Hertz, 1990;Sorg and Magistretti, 1991;Coopersmith and Leon, 1995), the action of b-AR agonists b-ARs in central metabolism and memory ME Gibbs et al was challenged with the glycogen phosphorylase inhibitor DAB that prevents glycogen breakdown (Andersen et al, 1999;Andersen and Westergaard, 2002). We have shown that administration of DAB interferes with memory processing (Gibbs et al, 2006a).…”

Section: -Ar Agonists Affect Memory Formation By Activating Glycogenomentioning

confidence: 87%

“…In contrast, none of these metabolic inhibitors affected the ability of the b 2 -AR agonist zinterol to consolidate weakly reinforced memory. This effect was counteracted by DAB, suggesting that zinterol acts by stimulating glycogenolysis (Nahorski et al, 1975;Magistretti, 1988;Subbarao and Hertz, 1990;Coopersmith and Leon, 1995). There was no interaction between CL316243 and DAB.…”

Section: Interactions Between B 2 -And B 3 -Ars and Glucose Metabolismmentioning

confidence: 94%

Role of β-Adrenoceptors in Memory Consolidation: β3-Adrenoceptors Act on Glucose Uptake and β2-Adrenoceptors on Glycogenolysis

Gibbs

Hutchinson

Summers

2007

Neuropsychopharmacol

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Noradrenaline, acting via b 2 -and b 3 -adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated b 3 -rather than b 2 -ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na + /energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with b 3 -AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with b 2 -AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) b 2 -and b 3 -ARs consolidate memory by different mechanisms; b 3 -ARs stimulate central glucose transport, whereas b 2 -ARs stimulate central glycogenolysis.

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“…This mode of activation is less rapid than that evoked by K + (Subbarao and Hertz, 1990) and is executed via specific subclasses of receptors and second messenger systems. For example, noradrenaline increases glycogen phosphorylase activity via protein kinase A activation in response to b-adrenergic receptor stimulation and by an increase in [Ca 2 + ] i in a 2 -adrenergic receptor stimulation.…”

Section: Fuel For Regulation Of Extracellular K + Concentration By Asmentioning

confidence: 97%

Energy Metabolism in Astrocytes: High Rate of Oxidative Metabolism and Spatiotemporal Dependence on Glycolysis/Glycogenolysis

Hertz

Peng

Dienel

2007

J Cereb Blood Flow Metab

Self Cite

526

573

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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 0 triphosphate (ATP). The proportion of cortical oxidative metabolism attributed to astrocytes (B30%) 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. Keywords: acetate; glucose metabolism; glutamate; neurotransmitters; potassium; pyruvate carboxylation Introduction Astrocytes are More Than HousekeepersRecent studies in many different fields have shown much more active roles of astrocytes in brain function than previously portrayed by their traditionally ascribed 'bystander or housekeeping' functions. Emerging roles of astrocytes include their interactions with the vasculature, neurons, and other astrocytes via signaling, biosynthetic, and transport processes to regulate blood flow, modulate impulse transmission, and synthesize and degrade glucose-derived neurotransmitters, for example, glutamate and g-aminobutyric acid (GABA) (Takano et al, 2006;Hertz and Zielke, 2004;Volterra and Meldolesi, 2005). All of these processes are energyrequiring or dependent on energy-related metabolic pathways, thereby directly linking astrocyte functions, energetics, and metabolite fluxes.The narrow astrocytic surface extensions (lamellae and filopodia, also called peripheral ast...

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Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes

Cited by 120 publications

References 33 publications

Glial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro

Glial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro

Role of β-Adrenoceptors in Memory Consolidation: β3-Adrenoceptors Act on Glucose Uptake and β2-Adrenoceptors on Glycogenolysis

Energy Metabolism in Astrocytes: High Rate of Oxidative Metabolism and Spatiotemporal Dependence on Glycolysis/Glycogenolysis

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