Comparison of lactate kinetics in vitro and in vivo is to be done

Glucose is an energy source for both neurons and glia in the adult brain but lactate, one of the monocarboxylic acids, being converted from pyruvate in astrocytes and supplied to neuron (“astrocyte-neurona lactate shuttle“) is an important energy fuel alternative to glucose as well. The role of exogenously added lactate as a viable energy substrate has remained controversial although recent data showed that exogenous lactate might be selectively taken up by neuron in intact rat brain (1) and that lactate works as an energy substrate supporting neuronal activity in presence or absence of glucose in vitro (2, 3) and in vivo (4, 5).

Notwithstanding experimental data supporting the existence of astrocyte-neurona lactate shuttle, the opponents (for contrasting views see 6, 7) basing on mathematical modeling, challenge the very phenomenon, strongly insisting on the following experiments that should be done before jumping to conclusions:

“In this perspective, we suggest that highly relevant experiments to help the experimental-theoretical interaction could be: (i) comparison of lactate kinetics in vitro, in vivo using biosensors, and in vivo using 1H MRS, in the same brain areas, and using various stimulation protocols; (ii) comparison, in vitro and in vivo, of NADH kinetics in astrocytes and neurons, and extracellular lactate and pH kinetics; (iii) this approach would be reinforced if the kinetics of oxygen concentration and intracellular pH and sodium were also measured, using for instance microelectrodes and fluorescent dyes.” (8)

  1. Yamada A, et. al., Lactate is an alternative energy fuel to glucose in neurons under anesthesia. NeuroReport 20:1538–1542, 2009
  2. Ivanov A, Mukhtarov M, Bregestovski P and Zilberter Y (2011). Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices. Front. Neuroenerg. 3:2.
  3. Kasischke K (2011). “Lactate fuels the neonatal brain”. Front. Neuroenerg. 3:4.
  4. Wyss M, Jolivet R, Buck A, Magistretti P, and Weber B. (2011). In Vivo Evidence for Lactate as a Neuronal Energy Source. J Neuroscience, 31(20):7477-7485
  5. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011 Mar 4; 144(5):810-23 Evaluation access here
  6. Korf J. 2006. Is brain lactate metabolized immediately after neuronal activity through the oxidative pathway? J Cereb Blood Flow Metab 26:1584–1586.
  7. Schurr A. 2006. Lactate: The ultimate cerebral oxidative energy substrate? J Cereb Blood Flow Metab 26:142–152.
  8. Aubert AS, Costalat R, Compartmentalization of Brain Energy Metabolism Between Glia and Neurons: Insights from Mathematical Modeling. GLIA 55:1272–1279, 2007
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