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Brain Glycogen Metabolism pp 311–329Cite as

Glycogen in Astrocytes and Neurons: Physiological and Pathological Aspects

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Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 23))

Abstract

Brain glycogen is stored mainly in astrocytes, although neurons also have an active glycogen metabolism. Glycogen has gained relevance as a key player in brain function. In this regard, genetically modified animals have allowed researchers to unravel new roles of this polysaccharide in the brain. Remarkably, mice in which glycogen synthase is abolished in the brain, and thus devoid of brain glycogen, are viable, thereby indicating that the polysaccharide in this organ is not a requirement for survival. While there was growing evidence supporting a role of glycogen in learning and memory, these animals have now confirmed that glycogen participates in these two processes.

The association of epilepsy with brain glycogen has also attracted attention. Analysis of genetically modified mice indicates that the relation between brain glycogen and epilepsy is complex. While the formation of glycogen aggregates clearly underlies epilepsy, as in Lafora Disease (LD), the absence of glycogen also favors the occurrence of seizures.

LD is a rare genetic condition that affects children. It is characterized by epileptic seizures and neurodegeneration, and it develops rapidly until finally causing death. Research into this disease has unveiled new aspects of glycogen metabolism. Animal models of LD accumulate polyglucosan bodies formed by aberrant glycogen aggregates, called Lafora bodies (LBs). The abolition of glycogen synthase (GS) prevents the formation of LBs and the development of LD, thereby indicating that glycogen accumulation underlies this disease and the associated symptoms, and thus establishing a clear relation between the accumulation of glycogen aggregates and the incidence of seizures.

Although it was initially accepted that LBs were essentially neuronal, it is now evident that astrocytes also accumulate polyglucosan aggregates in LD. However, the appearance and composition of these deposits differs from that observed in neurons. Of note, the astrocytic aggregates in LD models show remarkable similarities with corpora amylacea (CA), a type of polyglucosan aggregate observed in the brains of aged mice and humans. The abolition of GS in mice also impedes the formation of CA with age and at the same time prevents the formation of a number of protein aggregates associated with aging. Therefore CA may play a role in age-related neurological decline.

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Abbreviations

ANLS:

Astrocyte-neuron lactate shuttle

APBD:

Adult polyglucosan body disease

CAL:

Corpora amylacea-like

DAB:

1,4-dideoxy-1,4-imino-d-arabinitol

EPM2:

Progressive myoclonic epilepsy 2 GBE Glycogen branching enzyme

GP:

Glycogen phosphorylase

GS:

Glycogen synthase

HFS:

High-frequency stimulus

LBs:

Lafora bodies

LD:

Lafora disease

LFP:

Local field potential

LGS:

Liver glycogen synthase

LTP:

Long-term potentiation

MGS:

Muscle glycogen synthase

PGBs:

Polyglucosan bodies

PP1:

Protein phosphatase 1

PTG:

Protein targeting to glycogen

SAMP8:

Senescence accelerated mouse prone 8

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Authors and Affiliations

  1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona, Spain

    Jordi Duran & Joan J. Guinovart

  2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain

    Jordi Duran & Joan J. Guinovart

  3. Division of Neurosciences, Pablo de Olavide University, Seville, Spain

    Agnès Gruart, Juan Carlos López-Ramos & José M. Delgado-García

  4. Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Barcelona, Spain

    Joan J. Guinovart

Authors
  1. Jordi Duran
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  2. Agnès Gruart
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  3. Juan Carlos López-Ramos
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  4. José M. Delgado-García
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  5. Joan J. Guinovart
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Correspondence to Joan J. Guinovart .

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Editors and Affiliations

  1. Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark

    Mauro DiNuzzo

  2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

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Duran, J., Gruart, A., López-Ramos, J.C., Delgado-García, J.M., Guinovart, J.J. (2019). Glycogen in Astrocytes and Neurons: Physiological and Pathological Aspects. In: DiNuzzo, M., Schousboe, A. (eds) Brain Glycogen Metabolism. Advances in Neurobiology, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-030-27480-1_10

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