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: |
2021 |
Typology: |
1.01 - Original Scientific Article |
Organization: |
UL MF - Faculty of Medicine |
UDC: |
616-092 |
COBISS: |
52558339
|
ISSN: |
1532-1991 |
Views: |
61 |
Downloads: |
20 |
Average score: |
0 (0 votes) |
Metadata: |
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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 |