Close coupling between astrocytic and neuronal metabolisms to fulfill anaplerotic and energy needs in the rat brain.
Carbon metabolism in the rat brain was studied in animals anesthetized with a light dose of pentobarbital and in awake animals under morphine, which were infused with either [1-13C]glucose+acetate or glucose+[2-13C]acetate for various periods of time. Brain amino-acid enrichments in tissue extracts were determined by nuclear magnetic resonance (NMR) spectroscopy and their time evolution was analyzed by automatic fitting. Acetyl-coenzyme A C2 enrichment and ratio between pyruvate carboxylase and pyruvate dehydrogenase activity (PC/PDH) were determined from glutamate and glutamine labeling. The following results were obtained: (i) amino-acid enrichment patterns implied metabolic compartmentation and occurrence of the glutamate-glutamine cycle; (ii) kinetics of aspartate, GABA, and glutamate labeling from [1-13C]glucose and of glutamine labeling from [2-13C]acetate indicated a twofold higher metabolic activity in awake than in anesthetized rat brain; (iii) evaluation of the contributions of the astrocytic and neuronal metabolisms to glutamine synthesis in both groups of rats indicated a coupling between neuronal tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle and glial TCA cycle; and (iv) analyzing the extrapolations back to time zero and the steady-state values of PC/PDH indicated a close coupling between PC activity and both astrocytic and neuronal TCA cycles. All these results suggest a cooperative-like behavior of astrocytic and neuronal metabolisms to fulfill the anabolic and energy needs linked to brain activation.
Serres
Sébastien
S
Unité de Résonance Magnétique des Systèmes Biologiques, UMR 5536, CNRS-Université Victor Segalen, Bordeaux, France. sebastien.serres@dpag.ox.ac.uk
Raffard
Gérard
G
Franconi
Jean-Michel
JM
Merle
Michel
M
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003243:Consciousness; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D005973:Glutamine; D018698:Glutamic Acid; D005947:Glucose