Food for thought
Article first published online: 1 MAR 2012
© 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society
The Journal of Physiology
Volume 590, Issue 5, page 1013, March 2012
How to Cite
Secher, N. H. and Rasmussen, P. (2012), Food for thought. The Journal of Physiology, 590: 1013. doi: 10.1113/jphysiol.2011.224337
- Issue published online: 1 MAR 2012
- Article first published online: 1 MAR 2012
Cerebral metabolism depends on carbohydrate and because brain glycogen stores are small, the brain is thought to require continuous provision of glucose, as demonstrated during hypoglycaemia in diabetic patients and healthy subjects during prolonged exercise (Nybo et al. 2003). This view that cerebral metabolism is exclusively secured by blood glucose is now challenged by Matsui et al. (2011, 2012), in recent issues of The Journal of Physiology, who demonstrated that brain glycogen plays a central role also during exercise.
Indirect evidence that cerebral metabolism may become affected, even though blood glucose is maintained, was provided by brain release of interleukin 6 (IL-6) during and after prolonged exercise (Nybo et al. 2002; Rasmussen et al. 2011) but not during incremental exercise to exhaustion (Dalsgaard et al. 2004). Since administration of glucose during exercise blunts release of IL-6 from muscles (Febbraio et al. 2003), it is likely that brain IL-6 release indicates use of glycogen. For skeletal muscles, exercise reduces substrate availability since glycogen is used (Bergström & Hultman, 1966) and in contrast to the common dogma for the brain, the glycogen deposit is not trivial. Glycogen levels are at least 6 mm (glycosyl units) for white and grey matter and 13 mm in the hippocampus in humans (Dalsgaard et al. 2007). Considering that brain glycogen is confined to astrocytes (Pellerin & Magistretti, 2011), the cell concentration approaches the levels found in skeletal muscles and glycogen could be important for immediate provision of energy to the neurons during cerebral activation.
In support of this, brain glycogen decreases during exercise as seen in muscles. Rasmussen et al. (2011) addressed the relationship between regional distribution of brain glycogen and the expression of IL-6 mRNA in mice. Confirming observations from humans and pigs (Dalsgaard et al. 2007), the glycogen level was largest in the hippocampus and, as postulated, the hippocampus expression of IL-6 mRNA was lower than in other parts of the brain. Similarly, during exercise there was little change in these variables for cortex and cerebellum but for hippocampus, glycogen was reduced while the IL-6 mRNA expression increased. Exercise is also associated with a ∼50% reduction in the very precisely determined brain glycogen content in the rat (Matsui et al. 2011) and a decrease in glycogen could influence the ability of the animal to continue a given task and thereby contribute to the development of central fatigue. The unique observation by Bergström & Hultman (1966) was that over 3 days following exercise, muscle glycogen is doubled. Inspired by that finding, Matsui et al. (2012) now find that this increase in muscle glycogen following glycogen depletion due to exercise (so-called supercompensation) also manifests in the brain and, remarkably, develops faster than for skeletal muscle. Not only does the brain demonstrate glycogen supercompensation, but also the post-exercise increase in brain glycogen was most pronounced for those regions of the brain exposed to the largest decrease in glycogen during exhaustive exercise.
Subjects terminate exercise when muscle glycogen reaches a critical low level. Similarly, Matsui et al. (2012) consider that supercompensation of brain glycogen prepares the animal for prolonged exercise. This hypothesis needs to be evaluated and it remains to be established why there appears to be an inverse relationship between brain (and muscle) glycogen and IL-6, not disregarding a role for, for example, serotonin and nordarenaline in central fatigue. Since there is no reason to believe that exercise represents a special case of cerebral activation, the important message of the paper by Matsui et al. (2012) is that any type of cerebral activation is associated with a decrease in the relevant regional level of glycogen and that brain glycogen, therefore, represents the immediate fuel for thought.
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