Astrocytic glycogen metabolism in the healthy and diseased brain

Bak, Lasse K.; Walls, Anne B.; Schousboe, Arne; Waagepetersen, Helle S.

doi:10.1074/jbc.r117.803239

Cited by 113 publications

(95 citation statements)

References 96 publications

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“…Despite the energetically inefficient process, muscles and astrocytes have been reported to utilize glycogen to produce lactate during periods of high energy demand (Shulman, Hyder, & Rothman, ; Shulman & Rothman, ). This glycogen shunt process has the advantage of providing lactate more rapidly than glycolysis, hence may be more suitable for transient energy demands (for a review, Bak, Walls, Schousboe, & Waagepetersen, ). Localization of glycogen in perisynaptic astrocytic processes underscores the feasibility of on‐demand transcellular energy provision.…”

Section: Hippocampal Glycogen Usagesmentioning

confidence: 99%

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Glycogen distribution in mouse hippocampus

Hirase

Akther

Wang

et al. 2019

J of Neuroscience Research

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The hippocampus is a limbic structure involved in the consolidation of episodic memory. In the recent decade, glycogenolysis in the rodent hippocampus has been shown critical for synaptic plasticity and memory formation. Astrocytes are the primary cells that store glycogen which is subject to degradation in hypoglycemic conditions. Focused microwave application to the brain halts metabolic activities, and therefore preserves brain glycogen. Immunohistochemistry against glycogen on focused microwave‐assisted brain samples is suitable for both macroscopic and microscopic investigation of glycogen distribution. Glycogen immunohistochemistry in the hippocampus showed a characteristic punctate signal pattern that depended on hippocampal layers. In particular, the hilus is the most glycogen‐rich subregion of the hippocampus. Moreover, large glycogen puncta (>0.5 µm in diameter) observed in neuropil areas are organized in a patchy pattern consisting of puncta‐rich and ‐poor astrocytes. These observations are discussed with respect to distinct hippocampal neural activity states observed in live animals.

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Section: Hippocampal Glycogen Usagesmentioning

confidence: 99%

“…This glycogen shunt process has the advantage of providing lactate more rapidly than glycolysis, hence may be more suitable for transient energy demands (for a review, Bak, Walls, Schousboe, & Waagepetersen, 2018). Localization of glycogen in perisynaptic astrocytic processes underscores the feasibility of on-demand transcellular energy provision.…”

Section: ;mentioning

confidence: 99%

Glycogen distribution in mouse hippocampus

Hirase

Akther

Wang

et al. 2019

J of Neuroscience Research

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“…Regulation of glycogen metabolism is the prototypical example of cAMP/PKA‐mediated signaling in many biochemistry textbooks. For detailed reviews on the Ca 2+ and cAMP‐mediated regulation of glycogen metabolism including both receptor and non‐receptor mediated aspects, please see Bak, Walls, Schousboe, and Waagepetersen () and Obel et al (). The enzyme phosphorylase kinase, which activates the glycogen‐degrading enzyme glycogen phosphorylase (GP) via phosphorylation, is activated by Ca 2+ directly (positive allosteric modulator) and by PKA‐mediated phosphorylation (Figure ).…”

Section: Multiple Roles Of Camp Signaling In Astrocytesmentioning

confidence: 99%

“…The enzyme phosphorylase kinase, which activates the glycogen‐degrading enzyme glycogen phosphorylase (GP) via phosphorylation, is activated by Ca 2+ directly (positive allosteric modulator) and by PKA‐mediated phosphorylation (Figure ). The relative importance of Ca 2+ ‐ and cAMP/PKA‐mediated engagement of glycogen breakdown is not entirely clear and somewhat divergent data have been published (reviewed in Bak et al, ; Obel et al, ). Thus, primary signals causing secondary cAMP or Ca 2+ signals may all trigger breakdown of glycogen although due to the compartmentalization of the signals (and possibly intracellular location of glycogen) it is unlikely that they all do.…”

Section: Multiple Roles Of Camp Signaling In Astrocytesmentioning

confidence: 99%

Aspects of astrocytic cAMP signaling with an emphasis on the putative power of compartmentalized signals in health and disease

Reuschlein

Jakobsen

Mertz

et al. 2019

Glia

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This review discusses aspects of known and putative compartmentalized 3′,5′‐cyclic adenosine monophosphate (cAMP) signaling in astrocytes, a cell type that has turned out to be a key player in brain physiology and pathology. cAMP has attracted less attention than Ca2+ in recent years, but could turn out to rival Ca2+ in its potential to drive cellular functions and responses to intra— and extracellular cues. Further, Ca2+ and cAMP are known to engage in extensive crosstalk and cAMP signals often take place within subcellular compartments revolving around multi‐protein signaling complexes; however, we know surprisingly little about this in astrocytes. Here, we review aspects of astrocytic cAMP signaling, provide arguments for an increased interest in this subject, suggest possible future research directions within the field, and discuss putative drug targets.

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“…In the mature brain, glycogen is primarily located in astrocytes (Cataldo & Broadwell, 1986). Although glucose from the blood stream is calorically sufficient to fuel brain's energetic requirements, brain glycogen stores have a prominent physiological role (Bak, Walls, Schousboe, & Waagepetersen, 2018). It has been for a long time known to be present in astrocytic processes that are adjacent to synapses (Koizumi & Shiraishi, 1970;Phelps, 1972).…”

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Glycogen metabolism is impaired in the brain of male type 2 diabetic Goto‐Kakizaki rats

Soares

Nissen

García-Serrano

et al. 2019

J of Neuroscience Research

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Diabetes impacts the central nervous system predisposing to cognitive decline. While glucose is the main source of energy fueling the adult brain, brain glycogen is necessary for adequate neuronal function, synaptic plasticity and memory. In this study, we tested the hypothesis that brain glycogen metabolism is impaired in type 2 diabetes (T2D). 13C magnetic resonance spectroscopy (MRS) during [1‐13C]glucose i.v. infusion was employed to detect 13C incorporation into whole‐brain glycogen in male Goto‐Kakizaki (GK) rats, a lean model of T2D, and control Wistar rats. Labeling from [1‐13C]glucose into brain glycogen occurred at a rate of 0.25 ± 0.12 and 0.48 ± 0.22 µmol/g/h in GK and Wistar rats, respectively (p = 0.028), despite similar brain glycogen concentrations. In addition, the appearance of [1‐13C]glucose in the brain was used to evaluate glucose transport and consumption. T2D caused a 31% reduction (p = 0.031) of the apparent maximum transport rate (Tmax) and a tendency for reduced cerebral metabolic rate of glucose (CMRglc; −29%, p = 0.062), indicating impaired glucose utilization in T2D. After MRS in vivo, gas chromatography‐mass spectrometry was employed to measure regional 13C fractional enrichment of glucose and glycogen in the cortex, hippocampus, striatum, and hypothalamus. The diabetes‐induced reduction in glycogen labeling was most prominent in the hippocampus and hypothalamus, which are crucial for memory and energy homeostasis, respectively. These findings were further supported by changes in the phosphorylation rate of glycogen synthase, as analyzed by Western blotting. Altogether, the present results indicate that T2D is associated with impaired brain glycogen metabolism.

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Astrocytic glycogen metabolism in the healthy and diseased brain

Cited by 113 publications

References 96 publications

Glycogen distribution in mouse hippocampus

Glycogen distribution in mouse hippocampus

Aspects of astrocytic cAMP signaling with an emphasis on the putative power of compartmentalized signals in health and disease

Glycogen metabolism is impaired in the brain of male type 2 diabetic Goto‐Kakizaki rats

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