Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.
The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.
Sickmann
Helle M
HM
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Walls
Anne B
AB
Schousboe
Arne
A
Bouman
Stephan D
SD
Waagepetersen
Helle S
HS
D000818:Animals; D001089:Arabinose / Q000494:pharmacology; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D003627:Data Interpretation, Statistical; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism* / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D050113:Imino Furanoses / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010654:Phenylbutyrates / Q000494:pharmacology; D013402:Sugar Alcohols / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
C504712:3-(5-chloroindole-2-carbonyl)amino-2-hydroxy-4-phenylbutyric acid N-methyl-N-methoxyamide; D050113:Imino Furanoses; D007211:Indoles; D027501:Monocarboxylic Acid Transporters; D010654:Phenylbutyrates; D013402:Sugar Alcohols; C058137:1,4-dideoxy-1,4-iminoarabinitol; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D006003:Glycogen; D001089:Arabinose