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Non-signalling energy use in the brain - PubMed

  • ️Thu Jan 01 2015

Review

Non-signalling energy use in the brain

Elisabeth Engl et al. J Physiol. 2015.

Abstract

Energy use limits the information processing power of the brain. However, apart from the ATP used to power electrical signalling, a significant fraction of the brain's energy consumption is not directly related to information processing. The brain spends just under half of its energy on non-signalling processes, but it remains poorly understood which tasks are so energetically costly for the brain. We review existing experimental data on subcellular processes that may contribute to this non-signalling energy use, and provide modelling estimates, to try to assess the magnitude of their ATP consumption and consider how their changes in pathology may compromise neuronal function. As a main result, surprisingly little consensus exists on the energetic cost of actin treadmilling, with estimates ranging from < 1% of the brain's global energy budget up to one-half of neuronal energy use. Microtubule treadmilling and protein synthesis have been estimated to account for very small fractions of the brain's energy budget, whereas there is stronger evidence that lipid synthesis and mitochondrial proton leak are energetically expensive. Substantial further research is necessary to close these gaps in knowledge about the brain's energy-expensive non-signalling tasks.

© 2015 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

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Figures

Figure 1
Figure 1. Energy budget for the grey matter adapted from Harris & Attwell 2012)

For the grey matter, Attwell & Laughlin (2001) and Harris & Attwell (2012) assumed that ‘housekeeping’ processes account for 25% of total energy use (right diagram shows numbers from Harris & Attwell, 2012). Assuming the same housekeeping energy use per unit volume, Harris & Attwell (2012) showed that this would be ∼60% of total energy use in the white matter where far less energy is spent on synaptic transmission and action potentials. Under the umbrella term of ‘housekeeping’, the brain carries out many distinct processes (left). Their relative contributions to the total energy budget, and the balance of ‘housekeeping’ and signalling energy expenditure in the brain, are reviewed.

Figure 2
Figure 2. Continuous ATP-dependent treadmilling of the actin cytoskeleton

Exchanging the ADP bound to free G-actin monomers for ATP enables them to bind (predominantly) to the barbed end of actin filaments, causing them to grow. The bound ATP is subsequently hydrolysed and ADP-bound actin monomers can then detach from the pointed end of the filament, completing the cycle.

Figure 3
Figure 3. The stages of GTP-dependent dynamic instability in microtubules

Tubulin molecules binding GTP attach to an existing filament and form a semi-stable GTP cap. Subsequently, a ‘catastrophe’ involving hydrolysis (to GDP) of the bound GTP occurs, which leads to the detachment of individual heterodimers and thus the sudden shrinkage of the microtubule strand. In the ‘rescue’, GDP is then exchanged for GTP at individual free heterodimers, which are then ready to be re-added to the semi-stable shrunken filament.

Figure 4
Figure 4. Different stages of microglial morphology depending on their task

All microglial stages, as well as the transitions between them, are highly dependent on actin turnover. In the misleadingly-named ‘resting’ form, their processes continually move to scan the brain parenchyma, requiring constant restructuring of the actin cytoskeleton. In response to various signals, such as ATP released from damaged cells, microglia become activated. They extend processes towards the site of injury (schematised as a dying cell in red) and retract those that were facing away from the damaged area (Davalos et al. 2005). Prior to travelling to a site of cell or tissue damage and performing phagocytosis, microglia withdraw their processes entirely and translocate, after the formation of new highly motile protrusions (Stence et al. 2001).

Figure 5
Figure 5. An updated tentative summary of the brain's non-signalling energy expenditure

Current theoretical estimates and experimental data assessing the contribution of each ‘housekeeping’ process to the brain's total energy budget are inconclusive for many processes, varying widely in some cases. Further research is needed to fill these gaps, and the 40% value shown (right), for the whole brain according to Astrup et al. (a), as opposed to the 25% assumed for grey matter in Fig.1, is quite uncertain. Left: estimates for each ‘housekeeping’ process’ percentage share of total brain energy expenditure are given as a summary of this review. E, data for the estimate were obtained experimentally; M, an estimate was calculated from models based on experimental data (often from several animal models, ages, etc.); E + M a combination, where a relatively small leap from experimental data to the final estimate was required. For quick reference, processes are labelled as energetically inexpensive (green), expensive (orange) or of as yet uncertain energy consumption because of contradictory evidence or a lack of data (grey).

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