An imaging study on the contribution of glial energy metabolism to the neuroprotective effect of ketone bodies
Final Report Abstract
In summary, our main 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 are involved in orchestrating the neuroprotective effect of ketone bodies and are in register with the recent observation that GLUT1 reductions in the blood brain barrier -but not in astrocytes- exacerbate neurological abnormalities in a mouse model of Alzheimer´s disease. Therefore, astrocytic glycolysis may be considered a possible therapeutic target for neurological diseases.
Publications
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(2014) Higher transport and metabolism of glucose in astrocytes compared to neurons: A multiphoton study of hippocampal and cerebellar tissue slices. Cereb Cortex 24, 222-231
Jakoby, P., Schmidt, E., Ruminot, I., Gutierrez, R., Barros, L.F. & Deitmer, J.W.
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(2015) Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate. Journal of Cerebral Blood Flow & Metabolism, Vol 36, Issue 10, pp. 1813 - 1822
Valdebenito, R., Ruminot, I., Garrido-Gerter, P. Fernández-Moncada, I., Forero-Quintero, L., Alegría, K., Becker, H.M., Deitmer, J.W.& Barros, L.F.
