Cytochemical identification of cerebral glycogen and glucose‐6‐phosphatase activity under normal and experimental conditions: I. Neurons and glia

Cataldo, Anne M.; Broadwell, Richard D.

doi:10.1002/jemt.1060030406

Cited by 170 publications

(141 citation statements)

References 57 publications

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“…No attempts were made to quantify the glycogen seen in this manner. These results agreed with previous studies on other neural areas (Cataldo and Broadwell, 1986;Magistretti et al, 1993).…”

Section: Ultrastructural Identification Of Astrocytic Glycogen In Thesupporting

confidence: 94%

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Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

Wender

Brown²,

Fern³

et al. 2000

J. Neurosci.

340

339

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We tested the hypothesis that astrocytic glycogen sustains axon function during and enhances axon survival after 60 min of glucose deprivation. Axon function in the rat optic nerve (RON), a CNS white matter tract, was monitored by measuring the area of the stimulus-evoked compound action potential (CAP). Switching to glucose-free artificial CSF (aCSF) had no effect on the CAP area for ϳ30 min, after which the CAP rapidly failed. Exposure to glucose-free aCSF for 60 min caused irreversible injury, which was measured as incomplete recovery of the CAP. Glycogen content of the RON fell to a low stable level 30 min after glucose withdrawal, compatible with rapid use in the absence of glucose. An increase of glycogen content induced by high-glucose pretreatment increased the latency to CAP failure and improved CAP recovery. Conversely, a decrease of glycogen content induced by norepinephrine pretreatment decreased the latency to CAP failure and reduced CAP recovery. To determine whether lactate represented the fuel derived from glycogen and shuttled to axons, we used the lactate transport blockers quercetin, ␣-cyano-4-hydroxycinnamic acid (4-CIN), and p-chloromercuribenzene sulfonic acid ( pCMBS). All transport blockers, when applied during glucose withdrawal, decreased latency to CAP failure and decreased CAP recovery. The inhibitors 4-CIN and pCMBS, but not quercetin, blocked lactate uptake by axons. These results indicated that, in the absence of glucose, astrocytic glycogen was broken down to lactate, which was transferred to axons for fuel. Key words: astrocytes; ␣-cyano-4-hydroxycinnamate; glucose; hypoglycemia; lactate; p-chloromercuribenzene sulfonic acid; quercetin; rat optic nerveThe function of brain glycogen is not well understood. Glycogen turns over rapidly in the brain, however, and turnover is enhanced when adjacent neural activity is increased (Orkand et al., 1973;Pentreath and Kai-Kai, 1982;Swanson et al., 1992). It is appealing to imagine that glycogen might serve to provide fuel to the brain when glucose is in short supply. Indeed, astrocytic glycogen in vitro is degraded rapidly when glucose is withdrawn (Dringen et al., 1993), and glycogen falls rapidly in vivo during ischemia, with a time course that is closely related to the depletion of ATP and the accumulation of lactate (Swanson et al., 1989a). These observations are consistent with the action of glycogen as a fuel source during glucose shortage, but they do not prove this hypothesis. Glycogen content varies by a factor of two or more between brain regions [it is highest in the brainstem and cerebellum and lowest in the striatum and white matter (Swanson et al., 1989a)]. Energy metabolism also varies significantly between different brain regions (Sokoloff et al., 1977). Therefore, glycogen could be more protective against glucose depletion in some areas than in others.Given all of the above, it is natural to wonder whether glycogen can enhance the survival and function of brain tissue in the absence of glucose. Surprisingly, only a single st...

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“…No attempts were made to quantify the glycogen seen in this manner. These results agreed with previous studies on other neural areas (Cataldo and Broadwell, 1986;Magistretti et al, 1993).…”

Section: Ultrastructural Identification Of Astrocytic Glycogen In Thesupporting

confidence: 94%

“…Brain glycogen, localized almost exclusively in astrocytes (see Fig. 2), is a prime candidate to fill this role (Cataldo and Broadwell, 1986;Magistretti et al, 1993). The preservation of the CAP in glucose-free aCSF was not attributable to persistent glucose within the tissue.…”

Section: Discussionmentioning

confidence: 98%

Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

Wender

Brown²,

Fern³

et al. 2000

J. Neurosci.

340

339

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“…2 Here, we show that glycogen is also present in immature cultured neurons and that its presence might have been overlooked because of its low concentration compared with that found in astrocytes. 40 This reinterpretation of the panorama has only been possible as a result of the optimization of the method used for glycogen measurement, which greatly increased its sensitivity.…”

Section: Discussionmentioning

confidence: 69%

Neurons Have an Active Glycogen Metabolism that Contributes to Tolerance to Hypoxia

Sáez

Durán

Sinadinos

et al. 2014

J Cereb Blood Flow Metab

177

165

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Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

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“…Besides, EGCs characteristically possess a large membrane surface relative to their small size, which is consistent with their potential role in regulating metabolite exchanges between enteric neurons and the blood supply (Gershon and Bursztajn, 1978;Hanani and Reichenbach, 1994). Secondly, as EGCs are rich in glycogen granules, they may constitute a major source of glucose for enteric neurons, similar to that provided by astrocytes to CNS neurons (Koizumi, 1974;Cataldo and Broadwell, 1986). Thirdly, EGCs have recently been shown to be the only cells within the ENS that are immunoreactive for L-arginine (Nagahama et al, 2001), a substrate required for the nitric oxide (NO) synthesis.…”

Section: Neuroprotective and Neuromodulatory Functions Of Egcmentioning

confidence: 69%

Role of enteric glial cells in inflammatory bowel disease

Cabarrocas

Savidge

Liblau

2002

Glia

159

154

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Enteric glial cells (EGCs) represent an extensive but relatively poorly described cell population within the gastrointestinal tract. Accumulating data suggest that EGCs represent the morphological and functional equivalent of CNS astrocytes within the enteric nervous system (ENS). The EGC network has trophic and protective functions toward enteric neurons and is fully implicated in the integration and the modulation of neuronal activities. Moreover, EGCs seem to be active elements of the ENS during intestinal inflammatory and immune responses, sharing with astrocytes the ability to act as antigen-presenting cells and interacting with the mucosal immune system via the expression of cytokines and cytokine receptors. Transgenic mouse systems have demonstrated that specific ablation of EGC by chemical ablation or autoimmune T-cell targeting induces an intestinal pathology that shows similarities to the early intestinal immunopathology of Crohn's disease. EGCs may also share with astrocytes the ability to regulate tissue integrity, thereby postulating that similar interactions to those observed for the blood-brain barrier may also be partly responsible for regulating mucosal and vascular permeability in the gastrointestinal tract. Disruption of the EGC network in Crohn's disease patients may represent one possible cause for the enhanced mucosal permeability state and vascular dysfunction that are thought to favor mucosal inflammation. GLIA 41:81-93, 2003.

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Cytochemical identification of cerebral glycogen and glucose‐6‐phosphatase activity under normal and experimental conditions: I. Neurons and glia

Cited by 170 publications

References 57 publications

Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

Neurons Have an Active Glycogen Metabolism that Contributes to Tolerance to Hypoxia

Role of enteric glial cells in inflammatory bowel disease

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