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      Non-signalling energy use in the brain : Non-signalling energy use in the brain

      1 , 1
      The Journal of Physiology
      Wiley

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          Abstract

          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.

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          Most cited references80

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          Cellular motility driven by assembly and disassembly of actin filaments.

          Motile cells extend a leading edge by assembling a branched network of actin filaments that produces physical force as the polymers grow beneath the plasma membrane. A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion. Signaling pathways converging on WASp/Scar proteins regulate the activity of Arp2/3 complex, which mediates the initiation of new filaments as branches on preexisting filaments. After a brief spurt of growth, capping protein terminates the elongation of the filaments. After filaments have aged by hydrolysis of their bound ATP and dissociation of the gamma phosphate, ADF/cofilin proteins promote debranching and depolymerization. Profilin catalyzes the exchange of ADP for ATP, refilling the pool of ATP-actin monomers bound to profilin, ready for elongation.
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            The P2Y12 receptor regulates microglial activation by extracellular nucleotides.

            Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a G(i)-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking G(i)-coupled P2Y(12) receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry(12)(-/-) mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y(12) expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y(12) is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.
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              Dynamic instability of microtubule growth.

              We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
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                Author and article information

                Journal
                The Journal of Physiology
                J Physiol
                Wiley
                00223751
                August 15 2015
                August 15 2015
                March 11 2015
                : 593
                : 16
                : 3417-3429
                Affiliations
                [1 ]Department of Neuroscience; Physiology & Pharmacology; University College London; London WC1E 6BT UK
                Article
                10.1113/jphysiol.2014.282517
                ad4477b5-b45e-48b2-ab37-306f5453261c
                © 2015

                http://doi.wiley.com/10.1002/tdm_license_1.1

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