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Séminaire impromptu - Claude MessierAlternate fuels for the brain: Impact of intraperitoneal glucose, fructose, galactose, lactate, pyruvate, beta-hydroxybutyrate and insulin on glucose and lactate levels in the brain antechamber.

Abstract :


 As most textbooks state, glucose is the main fuel of the brain. The Neuron-to-Astrocyte-Lactate Shuttle (NALS) suggests that the lactate is a by-product product of neuronal glucose.
Conversely, a competing hypothesis by Pellerin and Magistretti, the Astrocyte-to-Neuron-Lactate Shuttle (ANLS) hypothesis proposes that peripheral glucose is taken up by astrocytic end feet, converted to lactate and released in the extracellular space and used by neurons as a source of metabolic fuel. Within this context, we examine the changes in lactate and glucose in the extracellular fluid of the motor cortex following intraperitoneal (ip) injections of glucose, fructose, galactose, lactate, pyruvate, beta-hydroxybutyrate and insulin.

Electrochemical electrodes (Pinnacle Tech.) that detect glucose or lactate were inserted in the left or right motor cortex of CD-1 male mice so that glucose and lactate could be measured simultaneously. In separate experiments, we also measured glucose and lactate levels in tail blood using portable glucose and lactate meters. Glucose and lactate levels were measured before and after intraperitoneal injections and results were expressed as a percentage of pre-injection values. Intraperitoneal 2 g/kg glucose, fructose, lactate, pyruvate, beta-hydroxybutyrate and to a much lesser extent, galactose all raised cortical extracellular glucose levels (200%) while intraperitoneal insulin reduced cortex extracellular glucose and lactate equally. As expected, ip glucose raised and ip insulin reduced blood glucose.
All ip injections raised blood lactate levels. In contrast, extracellular cortical lactate levels remained unchanged except for a transitory raise following ip lactate and a 40% decrease following ip insulin. The present methodology does not allow determining the origin of the extracellular changes in glucose and lactate. However, the data indicates that blood increases of many potential metabolic substrates lead to increases in brain extracellular glucose but only the ip injection of lactate produced a significant but transient brain extracellular lactate increase. The observation that the ip injection of all substrates increased blood lactate raise the possibility that the extracellular glucose increase in the brain is due to brain metabolism of circulating lactate.
However, the ip injection of 2g/kg of lactate does not lead to greater brain extracellular glucose. Interestingly, the extracellular glucose increase following the ip injection of glucose or lactate is almost immediate whereas the brain extracellular glucose increase is delayed following the ip injection of the other substrates.

Selected publications

Plastic changes in the astrocyte GLUT1 glucose transporter and beta-tubulin microtubule protein following voluntary exercise in mice. Allen A, Messier C.Behav Brain Res. 2013 Mar 1;240:95-102. doi: 10.1016/j.bbr.2012.11.025. Epub 2012 Nov 29.

Glucose regulation is associated with cognitive performance in young nondiabetic adults. Messier C, Awad-Shimoon N, Gagnon M, Desrochers A, Tsiakas M.Behav Brain Res. 2011 Sep 12;222(1):81-8. doi: 10.1016/j.bbr.2011.03.023. Epub 2011 Mar 21.

Effect of age and glucoregulation on cognitive performance. Messier C, Tsiakas M, Gagnon M, Desrochers A. J Clin Exp Neuropsychol. 2010 Oct;32(8):809-21. doi: 10.1080/13803390903540323. Epub 2010 Mar 5.