Anemari Horvat (Author), Marko Muhič (Author), Tina Smolič (Author), Ena Begić (Author), Robert Zorec (Author), Marko Kreft (Author), Nina Vardjan (Author)

Abstract

Astroglial aerobic glycolysis, a process during which d-glucose is converted to l-lactate, a brain fuel and signal, is regulated by the plasmalemmal receptors, including adrenergic receptors (ARs) and purinergic receptors (PRs), modulating intracellular Ca2+ and cAMP signals. However, the extent to which the two signals regulate astroglial aerobic glycolysis is poorly understood. By using agonists to stimulate intracellular [alpha]1-/[beta]-AR-mediated Ca2+/cAMP signals, [beta]-AR-mediated cAMP and P2R-mediated Ca2+ signals and genetically encoded fluorescence resonance energy transfer-based glucose and lactate nanosensors in combination with real-time microscopy, we show that intracellular Ca2+, but not cAMP, initiates a robust increase in the concentration of intracellular free d-glucose ([glc]i) and l-lactate ([lac]i), both depending on extracellular d-glucose, suggesting Ca2+-triggered glucose uptake and aerobic glycolysis in astrocytes. When the glycogen shunt, a process of glycogen remodelling, was inhibited, the [alpha]1-/[beta]-AR-mediated increases in [glc]i and [lac]i were reduced by %65 % and %30 %, respectively, indicating that at least %30 % of the utilization of d-glucose is linked to glycogen remodelling and aerobic glycolysis. Additional activation of [beta]-AR/cAMP signals aided to [alpha]1-/[beta]-AR-triggered [lac]i increase, whereas the [glc]i increase was unaltered. Taken together, an increase in intracellular Ca2+ is the prime mechanism of augmented aerobic glycolysis in astrocytes, while cAMP has only a moderate role. The results provide novel information on the signals regulating brain metabolism and open new avenues to explore whether astroglial Ca2+ signals are dysregulated and contribute to neuropathologies with impaired brain metabolism.

Keywords

astrocytes;aerobic glycolysis;d-glucose;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-092
COBISS: 52558339 Link will open in a new window
ISSN: 1532-1991
Views: 61
Downloads: 20
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Other data

Secondary language: Slovenian
Secondary keywords: astrociti;aerobna glikoliza;d-glukoza;
Type (COBISS): Article
Pages: str. 1-11
Issue: ǂVol. ǂ95
Chronology: May 2021
DOI: 10.1016/j.ceca.2021.102368
ID: 15956611