title: Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling.
abstract: In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na(+) influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na(+) influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current 'thinking paradigm'. This might be critical in subcellular domains during functional conditions associated with fast energetic demands.
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy. mauro.dinuzzo@roma1.infn.it
authors.forename: Mauro
authors.initials: M
authors.lastname: DiNuzzo
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangia
authors.forename: Bruno
authors.initials: B
authors.lastname: Maraviglia
authors.forename: Federico
authors.initials: F
authors.lastname: Giove
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D019344:Lactic Acid / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D019344:Lactic Acid; D006003:Glycogen
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