Correlation between brain glycogen and convulsive state in mice submitted to methionine sulfoximine

Bernard-Hélary, Katy; Lapouble, Eve; Ardourel, Maryvonne; Hevor, T. K.; Cloix, Jean‐François

doi:10.1016/s0024-3205(00)00756-6

Cited by 30 publications

(38 citation statements)

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“…Specifically, often but not always MSO-treated animals accumulated abnormal glycogen particles resembling aggregates of insoluble polyglucosans (Delorme and Hevor, 1985; Phelps, 1975). Those animals that did not synthesize abnormal glycogen were seizure-resistant (Bernard-Helary et al, 2000), a feature that turned out to depend on the capacity of metabolizing glycogen (Bernard-Helary et al, 2000; Folbergrova et al, 1996). Aggregates of insoluble polyglucosans in both astrocytes and neurons are also an hallmark of Lafora disease, one of the most severe form of myoclonus epilepsy (Tagliabracci et al, 2008; Valles-Ortega et al, 2011).…”

Section: How Excess Glutamate Can Impair K+ Homeostasismentioning

confidence: 99%

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

et al. 2014

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Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures.

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Section: How Excess Glutamate Can Impair K+ Homeostasismentioning

confidence: 99%

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

et al. 2014

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“…However, studies aimed at establishing such a role for glycogen failed to demonstrate consistent effects of seizures on glycogen levels (see Walling et al, 2007). The lack of success in correlating epilepsy and glycogen content has been evidenced by the finding that some animals subjected to MSO developed violent seizures without any variation in tissue glycogen (Bernard-Helary et al, 2000). Furthermore, animals capable of accumulating glycogen after MSO administration but before seizures exhibited different resistance to convulsions depending on whether they were able to utilize glycogen (Bernard-Helary et al, 2000).…”

Section: Synthesis Of Unmetabolizable Glycogen Is Correlated With Epimentioning

confidence: 99%

“…The lack of success in correlating epilepsy and glycogen content has been evidenced by the finding that some animals subjected to MSO developed violent seizures without any variation in tissue glycogen (Bernard-Helary et al, 2000). Furthermore, animals capable of accumulating glycogen after MSO administration but before seizures exhibited different resistance to convulsions depending on whether they were able to utilize glycogen (Bernard-Helary et al, 2000). Among MSO-treated animals, those that are seizure-prone accumulate aberrant glycogen particles, while those that are seizure-resistant exhibit normal-appearing glycogen particles whatever the change in glycogen levels (Delorme and Hevor, 1985; Folbergrova et al, 1996; Phelps, 1975).…”

Section: Synthesis Of Unmetabolizable Glycogen Is Correlated With Epimentioning

confidence: 99%

“…We have previously demonstrated using biophysical modeling that loss of affinity of this enzyme for glycogen inner chains is sufficient to produce aberrant particles (DiNuzzo, 2013). Overall, a defective capacity of degrading glycogen is likely to be proepileptogenic, regardless of whether its content is increased or not (Bernard-Helary et al, 2000). This argument might provide a common cue for epilepsy and LD (Boissonnet et al, 2013; Roach et al, 2012).…”

Section: Synthesis Of Unmetabolizable Glycogen Is Correlated With Epimentioning

confidence: 99%

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Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

et al. 2014

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Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K+ by astrocytes, thereby leading to increased extracellular K+ and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K+ homeostasis and increased susceptibility to seizures in epilepsy.

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“…Glycogen accumulation has been shown to delay the rate of propagation of spreading depression induced by insults such as high potassium or oxygen-glucose deprivation [127], which could play an important role in delaying the onset and spread of seizures [143, 144]. Thus, understanding the MSO-induced increase in glycogen levels could have potential therapeutic benefits.…”

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

Roles of Glutamine Synthetase Inhibition in Epilepsy

et al. 2012

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Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer’s disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.

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Correlation between brain glycogen and convulsive state in mice submitted to methionine sulfoximine

Cited by 30 publications

References 0 publications

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

Roles of Glutamine Synthetase Inhibition in Epilepsy

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