Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 36, Issue 10, Pages 1813-1822Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X15613955
Keywords
ATeam; FLII12Pglu700 mu Delta 6; Forster Resonance Energy Transfer microscopy; ketone bodies; pyronic
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Funding
- Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)-Chile
- Deutsche Forschungsgemeinschaft (DFG) [DFG-12, DE 231/25-1]
- Fondecyt [1130095]
- Chilean Government through Centers of Excellence Basal Financing Program of CONICYT
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The effectiveness of ketogenic diets and intermittent fasting against neurological disorders has brought interest to the effects of ketone bodies on brain cells. These compounds are known to modify the metabolism of neurons, but little is known about their effect on astrocytes, cells that control the supply of glucose to neurons and also modulate neuronal excitability through the glycolytic production of lactate. Here we have used genetically-encoded Forster Resonance Energy Transfer nanosensors for glucose, pyruvate and ATP to characterize astrocytic energy metabolism at cellular resolution. Our results show that the ketone body beta-hydroxybutyrate strongly inhibited astrocytic glucose consumption in mouse astrocytes in mixed cultures, in organotypic hippocampal slices and in acute hippocampal slices prepared from ketotic mice, while blunting the stimulation of glycolysis by physiological and pathophysiological stimuli. The inhibition of glycolysis was paralleled by an increased ability of astrocytic mitochondria to metabolize pyruvate. These results support the emerging notion that astrocytes contribute to the neuroprotective effect of ketone bodies.
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