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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

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Volume 29, Issue 8

Issues

Metabolic regulation of synaptic activity

Sergei V. Fedorovich
  • Corresponding author
  • Institute of Biophysics and Cell Engineering, Akademicheskaya St., 27, Minsk 220072, Belarus, e-mail:
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tatyana V. Waseem
Published Online: 2018-05-16 | DOI: https://doi.org/10.1515/revneuro-2017-0090

Abstract

Brain tissue is bioenergetically expensive. In humans, it composes approximately 2% of body weight and accounts for approximately 20% of calorie consumption. The brain consumes energy mostly for ion and neurotransmitter transport, a process that occurs primarily in synapses. Therefore, synapses are expensive for any living creature who has brain. In many brain diseases, synapses are damaged earlier than neurons start dying. Synapses may be considered as vulnerable sites on a neuron. Ischemic stroke, an acute disturbance of blood flow in the brain, is an example of a metabolic disease that affects synapses. The associated excessive glutamate release, called excitotoxicity, is involved in neuronal death in brain ischemia. Another example of a metabolic disease is hypoglycemia, a complication of diabetes mellitus, which leads to neuronal death and brain dysfunction. However, synapse function can be corrected with “bioenergetic medicine”. In this review, a ketogenic diet is discussed as a curative option. In support of a ketogenic diet, whereby carbohydrates are replaced for fats in daily meals, epileptic seizures can be terminated. In this review, we discuss possible metabolic sensors in synapses. These may include molecules that perceive changes in composition of extracellular space, for instance, ketone body and lactate receptors, or molecules reacting to changes in cytosol, for instance, KATP channels or AMP kinase. Inhibition of endocytosis is believed to be a universal synaptic mechanism of adaptation to metabolic changes.

Keywords: endocytosis; hypoglycemia; ketogenic diet; stroke; synapses

References

  • Achanta, L.B. and Rae, C.D. (2017). β-Hydroxybutirate in the brain: one molecule, multiple mechanisms. Neurochem. Res. 42, 35–49.Google Scholar

  • Alekseenko, A.A., Lemeshchenko, V.V., Pekun, T.G., Waseem, T.V., and Fedorovich, S.V. (2012). Glutamate-induced free radical formation in rat brain synaptosomes is not dependent on intrasynaptosomal mitochondria membrane potential. Neurosci. Lett. 513, 238–242.Google Scholar

  • Arakawa, T., Goto, T., and Okada, Y. (1991). Effect of ketone body (D-3-hydroxybutyrate) on neuronal activity and energy metabolism in hippocampal slices of the adult guinea pig. Neurosci. Lett. 130, 53–56.Google Scholar

  • Ashrafi, G., Wu, Z., Farrell, R.J., and Ryan, T.A. (2017). GLUT4 mobilization supports energetic demands of active synapses. Neuron 93, 606–615.Google Scholar

  • Ashrafi, G. and Ryan, T.A. (2017). Glucose metabolism in nerve terminals. Curr. Opin. Neurobiol. 45, 156–161.Google Scholar

  • Attwell, D. and Gibb, A. (2005). Neuroenergetic and the kinetic design of excitatory synapses. Nat. Rev. Neurosci. 6, 841–849.Google Scholar

  • Attwell, D. and Laughlin, S.B. (2001). An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. 21, 1133–1145.Google Scholar

  • Bancila, V., Nikonenko, I., Dunant, Y., and Bloc, A. (2004). Zinc inhibits glutamate release via activation of pre-synaptic KATP channels and reduces ischaemic damage in rat hippocampus. J. Neurochem. 90, 1243–1250.Google Scholar

  • Bergersen, L.H. (2015). Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. J. Cereb. Blood Flow Metab. 35, 176–185.Google Scholar

  • Blad, C.C., Tang, C., and Offermanns, S. (2012). G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat. Rev. Drug Discov. 11, 603–619.Google Scholar

  • Bolay, H., Gursoy-Ozdemir, Y., Sara, Y., Onur, R., Can, A., and Dalkara, T. (2002). Persistent defect in transmitter release and synapsin phosphorylation in central cortex after transient moderate ischemic injury. Stroke 33, 1369–1375.Google Scholar

  • Brennan, A.M., Suh, S.W., Won, S.J., Narasimhan, P., Kauppinen, T.M., Lee H., Edling, Y., Chan, P.H., and Swanson, R.A. (2009). NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat. Neurosci. 12, 857–863.Google Scholar

  • Brennan-Minella, A.M., Won, S.J., and Swanson, R.A. (2015). NADPH oxidase-2: linking glucose, acidosis, and excitotoxicity in stroke. Antioxid. Redox Signal. 22, 161–174.Google Scholar

  • Brown, M.B., Sullivan, P.G., and Geddes, J.W. (2006). Synaptic mitochondria are more susceptible to Ca2+ overload than nonsynaptic mitochondria. J. Biol. Chem. 281, 11658–11668.Google Scholar

  • Carriedo, S.G., Yin, H.Z., Sensi, S.L., and Weiss, J.H. (1998). Rapid Ca2+ entry through Ca2+-permeable AMPA/kainate channels triggers marked intracellular Ca2+ rises and consequent oxygen radical production, J. Neurosci. 18, 7727–7738.Google Scholar

  • Castro, M.A., Beltran, F.A., Brauchi, S., and Concha, I.I. (2009). A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid. J. Neurochem. 110, 423–440.Google Scholar

  • Choi, D.W. (1987). Ionic dependence of glutamate neurotoxicity. J. Neurosci. 7, 369–379.Google Scholar

  • Choi, D.W., Maulucci-Gedde, M., and Kriegstein, A.R. (1987). Glutamate neurotoxicity in cortical cell culture. J. Neurosci. 7, 357–368.Google Scholar

  • Coco, M., Caggia, S., Musumeci, G., Perciavalle, V., Graziano, A.C., Pannuzzo, G., and Cardile, V. (2013). Sodium L-lactate differentially affects brain-derived neurotrophic factor, inducible nitric oxide synthase, and heat shock protein 70 kDA production in human astrocytes and SH-SY5Y cultures. J. Neurosci. Res. 91, 313–320.Google Scholar

  • Correia, S.C. and Moreira, P.I. (2010). Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration? J. Neurochem. 112, 1–12.Google Scholar

  • Corti, O., Lesage, S., and Brice, A. (2011). What genetics tells us about the causes and mechanisms of Parkinson’s disease. Physiol. Rev. 91, 1161–1218.Google Scholar

  • Costantini, L.C., Barr, L.J., Vogel, J.L., and Henderson, S.T. (2008). Hypometabolism as a therapeutic target in Alzheimer’s disease. BMC Neurosci. 9, S16.Google Scholar

  • D’Amico, M., Samengo, I., and Martire, M. (2010). Effects of extracellular pH reductions on [3H]D-aspartate and [3H]noradrenaline release by presynaptic nerve terminals isolated from rat cerebral cortex. J. Neural. Transm. 117, 27–34.Google Scholar

  • DeKosky, S.T., Scheff, S.W., and Styren, S.D. (1996). Structural correlates of cognition in dementia: quantification and assessment of synaptic charge. Neurodegeneration 5, 417–421.Google Scholar

  • Dingledine, R., Borges, K., and Traynelis S.F. (1999). The glutamate receptor ion channels. Pharm. Rev. 51, 7–61.Google Scholar

  • Dittman, J. and Ryan, T.A. (2009). Molecular circuitry of endocytosis at nerve terminals. Annu. Rev. Cell Dev. Biol. 25, 133–160.Google Scholar

  • Drapeau, P. and Nachshen, D.A. (1988). Effects of lowering extracellular and cytosolic pH on calcium fluxes, cytosolic calcium levels, and transmitter release in presynaptic nerve terminals isolated from rat brain. J. Gen. Physiol. 91, 305–315.Google Scholar

  • Elliott, K.A.C., Greig, M.E., and Benoy, M.P. (1937). The metabolism of lactic and pyruvic acids in normal and tumour tissues. III Rat liver, brain and testis. Biochem. J. 31, 1003–1020.Google Scholar

  • Engl, E., Jolivet, R., Hall, C.N., and Attwell, D. (2017). Non-signalling energy use in the developing rat brain. J. Cereb. Blood Flow Metab. 37, 951–966.Google Scholar

  • Fedorovich, S.V., Aksentsev, S.L., Lyskova, T.I., Kaler, G.V., Fedulov, A.S., and Konev, S.V. (1997). Effect of acidosis on membrane potential and calcium transport in rat brain synaptosomes. Biofizika 42, 412–416 [In Russian].Google Scholar

  • Fedorovich, S.V., Kaler, G.V., and Konev, S.V. (2003). Effect of low pH on glutamate uptake and release in isolated presynaptic endings from rat brain. Neurochem. Res. 28, 715–721.Google Scholar

  • Fedorovich, S., Hofmeijer, J., van Putten, M.J.A.M., and Le Feber J., (2017a). Reduced synaptic vesicle recycling during hypoxia in cultured cortical neurons. Front. Cell. Neurosci. 11, 32.Google Scholar

  • Fedorovich, S.V., Waseem, T.V., and Puchkova, L.V. (2017b). Biogenetic and morphofunctional heterogeneity of mitochondra: the case of synaptic mitochondria. Rev. Neurosci. 28, 363–373.Google Scholar

  • Gano, L.B., Patel, M., and Rho, J.M. (2014). Ketogenic diets, mitochondria, and neurological diseases. J. Lipid Res. 55, 2211–2228.Google Scholar

  • Garbow, J.R., Doherty, J.M., Schugar, R.C., Travers, S., Weber, M.L., Wentz, A.E., Ezenwajiaku, N., Cotter, D.G., Brunt, E.M., and Crawford, P.A. (2011). Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. Am. J. Physiol. Gastrointest. Liver Physiol. 300, G956–G967.Google Scholar

  • Garcia de Arriba, S., Franke, H., Pissarek, M., Nieber, K., and Illes, P. (1999). Neuroprotection by ATP-dependent potassium channels in rat neocortical brain slices during hypoxia. Neurosci. Lett. 273, 13–16.Google Scholar

  • Giminez-Cassina, A., Martinez-Francois, J.R., Fisher, J.K., Szlyk, B., Polak, K., Wiwczar, J., Tanner, G.R., Lutas, A., Yellen, G., and Danial, N.N. (2012). BAD-dependent regulation of fuel metabolism and KATP channel activity confers resistance to epileptic seizures. Neuron 74, 719–730.Google Scholar

  • Greig, S.L. (2015). Memantine ER/doneprezil: a review in Alzheimer’s diseases. CNS Drugs 29, 963–970.Google Scholar

  • Guo, C., Zhang, Y.X., Wang, T., Zhong, M.L., Yang, Z.H., Hao, L.J., Chai, R., and Zhang, S., (2015). Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice. Front. Aging Neurosci. 7, 104.Google Scholar

  • Harris, J.J., Jolivet, R., and Attwell, D. (2012). Synaptic energy use and supply. Neuron 75, 762–777.Google Scholar

  • Hashim, S.A. and Vanltallie, T.B. (2014). Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J. Lipid. Res. 55, 1818–1826.Google Scholar

  • Hawkins, R.A., Williamson, D.H., and Krebs, H.A. (1971). Ketone-body utilization by adult and suckling rat brain in vivo. Biochem. J. 122, 13–18.Google Scholar

  • Hofmeijer, J. and van Putten, M.J.A.M. (2012). Ischemic cerebral damage. An appraisal of synaptic failure. Stroke 43, 607–615.Google Scholar

  • Holmgren, C.D., Mukhtarov, M., Malkov, A.E., Popova, I.Y., Bregestovski, P., and Zilberter, Y. (2010). Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. J. Neurochem. 112, 900–912.Google Scholar

  • Hrynevich, S.V., Pekun, T.G., Waseem, T.V., and Fedorovich, S.V. (2015). Influence of glucose deprivation on membrane potentials of plasma membranes, mitochondria and synaptic vesicles in rat brain synaptosomes. Neurochem. Res. 40, 1188–1196.Google Scholar

  • Hrynevich, S.V., Waseem, T.V., Hebert, A., Pellerin, L., and Fedorovich, S.V. (2016a). β-Hydroxybutirate supports synaptic vesicle cycling but reduces endocytosis and exocytosis in rat brain synaptosomes. Neurochem. Int. 93, 73–81.Google Scholar

  • Hrynevich, S.V., Waseem, T.V., and Fedorovich, S.V. (2016b). Ketogenic diet as a treatment option for different CNS diseases. Int. J. Neurol. Res. 2, 285–290.Google Scholar

  • Hsu, K.S., Liang, Y.C., and Huang, C.C. (2000). Influence of an extracellular acidosis on excitatory synaptic transmission and long-term potentiation in the CA1 region of rat hippocampal slices. J. Neurosci. Res. 62, 403–415.Google Scholar

  • Hua, Y., Woehler, A., Kahms, M., Haucke, V., Neher, E., and Klingauf, J. (2013). Blocking endocytosis enhances short-term synaptic depression under conditions of normal availability of vesicles. Neuron 80, 343–349.Google Scholar

  • Ikemoto, A., Bole, D.G., and Ueda, T. (2003). Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. J. Biol. Chem. 278, 5929–5940.Google Scholar

  • Ikonomidou, C. and Turski, L. (2012). Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol. 1, 383–386.Google Scholar

  • Isaev, N.K., Stelmashook, E.V., Dirnagl, U., Plotnikov, E.Y., Kuvshinova, E.A., and Zorov, D.B. (2008). Mitochondrial free radical production induced by glucose deprivation in cerebellar granule neurons. Biochemistry (Mosc.) 73, 149–155.Google Scholar

  • Izumi, Y., Ishii, K., Katsuki, H., Benz, A.M., and Zorumski, C.F. (1998). β-Hydroxybutirate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices. J. Clin. Invest. 101, 1121–1132.Google Scholar

  • Jiang, C., Sigworth, F.J., and Haddad, G.G. (1994). Oxygen deprivation activates an ATP-inhibitable K+ channel in substantia nigra neurons. J. Neurosci. 14, 5590–5602.Google Scholar

  • Julio-Amilpas, A., Montiel, T., Soto-Tinoco, E., Geronimo-Olvera, C., and Massieu, L. (2015). Protection of hypoglycemia-induced neuronal death by β-hydroxybutirate involves the preservation of energy levels and decreased production of reactive oxygen species. J. Cereb. Blood Flow Metab. 35, 851–860.Google Scholar

  • Kauppinen, R.A. and Nicholls, D.G. (1986). Synaptosomal bioenergetics. The role of glycolisis, pyruvate oxidation and responses to hypoglycaemia. Eur. J. Biochem. 158, 159–165.Google Scholar

  • Keating, D.J. (2008). Mitochondrial dysfunction, oxidative stress, regulation of exocytosis and their relevance to neurodegenerative diseases. J. Neurochem. 104, 298–305.Google Scholar

  • Kety, S.S. and Schmidt, C.F. (1946). The effects of active and passive hyperventilation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men. J. Clin. Invest. 25, 107–119.Google Scholar

  • Kisler, K., Nelson, A.R., Montagne, A., and Zlokovic, B.V. (2017). Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 18, 419–434.Google Scholar

  • Kononenko, N.L. and Haucke, V. (2015). Molecular mechanisms of presynaptic membrane retrieval and synaptic vesicle reformation. Neuron 85, 484–496.Google Scholar

  • Koppel, S.J. and Swerdlow, R.H. (2018). Neuroketotherapeutics: a modern review of a century-old therapy. Neurochem. Int. In press.Google Scholar

  • Kraig, R.P. and Chesler, M. (1990). Astrocytic acidosis in hyperglycemic and complete ischemia. J. Cereb. Blood Flow Metab. 10, 104–114.Google Scholar

  • Lafon-Cazal, M., Pietri S., Culcasi M., and Bockaert, J. (1993). NMDA-dependent superoxide production and neurotoxicity. Nature 364, 535–537.Google Scholar

  • Languren, G., Montiel, T., Julio-Amilpas, A., and Massieu, L. (2013). Neuronal damage and cognitive impairment associated with hypoglycemia: an integrated view. Neurochem. Int. 63, 331–343.Google Scholar

  • Lau, A. and Tymianski, M. (2010). Glutamate receptors, neurotoxicity and neurodegeneration. Eur. J. Physiol. 460, 525–542.Google Scholar

  • Lauritzen, K.H., Morland, C., Puchades, M., Holm-Hansen, S., Hagelin, E.M., Lauritzen, F., Attramadal, H., Storm-Mathisen, J., Gjedde, A., and Bergersen, L.H. (2014). Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb. Cortex 24, 2784–2795.Google Scholar

  • Le Feber, J., Erkamp, N., van Putten, M.J.A.M., and Hofmeijer, J. (2017). Loss and recovery functional connectivity in cultured cortical networks. J. Neurophysiol. 118, 394–403.Google Scholar

  • Lepeta, K., Lourenco, M.V., Schweitzer, B.C., Martino Adami, P.V., Banerjee, P., Catuara-Solarz, S., de La Fuente Revenga, M., Guilem, A.M., Haidar, M., Ijomone, O.M., et al. (2016). Synaptopathies: synaptic dysfunction in neurological disorder – A review from students to students. J. Neurochem. 138, 785–805.Google Scholar

  • Lee, D.Y., Xun, Z., Platt, V., Budworth, H., Canaria, C.A., and McMurray, C.T. (2013). Distinct pools of non-glycolytic substrates differentiate brain regions and prime region-specific responses of mitochondria. PLos One 8, E68831.Google Scholar

  • Levin, L.R. and Buck, J. (2015). Physiological roles of acid-base sensors. Annu. Rev. Physiol. 77, 347–362.Google Scholar

  • Levko, A.V., Aksentsev, S.L., Fedorovich, S.V., and Konev S.V. (1998). Effect of calcium on the energy status of rat brain synaptosomes under acidosis. Biochemistry (Mosc.) 63, 180–184.Google Scholar

  • Lewis, L.D., Ljunggren, B., Ratcheson, R.A., and Siesjo, B.K. (1974). Cerebral energy state in insulin-induced hypoglycemia, related to blood glucose and to EEG. J. Neurochem. 23, 673–679.Google Scholar

  • Lo, E.H., Dalkara, T., and Moskowitz, M.A. (2003). Mechanisms, challenges and opportunities in stroke. Nat. Rev. Neurosci. 4, 399–415.Google Scholar

  • Lores-Arnaiz, S. and Bustamante, J. (2011). Age-related alterations in mitochondrial physiological parameters and nitric oxide production in synaptic and non-synaptic brain cortex mitochondria. Neuroscience 188, 117–124.Google Scholar

  • Ludwig, M.-G., Vanek, M., Guerini, D., Gasser, J.A., Jones, C.E., Junker, U., Hofstetter, H., Wolf, R.M., and Seuwen, K. (2003). Proton-sensing G-protein-coupled receptors. Nature 425, 93–98.Google Scholar

  • Lund, T.M., Ploug, K.B., Iversen, A., Jensen, A.A., and Jansen-Olesen, I. (2015). The metabolic impact of β-hydroxybutyrate on neurotransmission: reduced glucolysis mediates changes in calcium responses and KATP channel receptor sensitivity. J. Neurochem. 132, 520–531.Google Scholar

  • Manwani, B. and McCullough, L.D. (2013). Function of the master energy regulator adenosine monophosphate-activated protein kinase in stroke. J. Neurosci. Res. 91, 1018–1029.Google Scholar

  • Mattson, M.P., Keller, J.N., and Begley, J.G. (1998). Evidence for synaptic apoptosis. Exp. Neurol. 153, 35–48.Google Scholar

  • Mattson, M.P. (2003). Excitotoxic and excitoprotective mechanisms. NeuroMol. Med. 3, 65–94.Google Scholar

  • Mattson, M.P. (2015). Late-onset dementia: a mosaic of prototypical pathologies modifiable by diet and lifestyle. Aging Mech. Dis. 1, 15003.Google Scholar

  • McDermott, A.B., Role, L.W., and Siegelbaum, S.A. (1999) Presynaptic ionotropic receptors and the control of transmitter release. Annu. Rev. Neurosci. 22, 443–485.Google Scholar

  • McKenna, M.C., Tildon, J.T., Stevenson, J.H., Boatright, R., and Huang, S. (1993). Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: differences revealed using aminooxyacetate. Dev. Neurosci. 15, 320–329.Google Scholar

  • McTaggart, J.S., Clark, R.H., and Ashcroft, F.M. (2010). The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet. J. Physiol. 588, 3201–3209.Google Scholar

  • Mink, J.W., Blumenschine, R.J., and Adams, D.B. (1981). Ratio of central nervous system to body metabolism in vertebrates: its constancy and functional basis. Am. J. Physiol. 241, R203–R212.Google Scholar

  • Moody, W. (1984). Effects of intracellular H+ on the electrical properties of excitable cells. Annu. Rev. Neurosci. 7, 257–278.Google Scholar

  • Morgenthaler, F.D., Kraftsik, R., Catsikas, S., Magistretti, P.J., and Chatton, J.-Y. (2006). Glucose and lactate are equally effective in energizing activity-dependent synaptic vesicle turnover in purified cortical neurons. Neuroscience 141, 157–165.Google Scholar

  • Mosienko, V., Teschemacher, A.G., and Kasparov, S. (2015). Is L-lactate a novel signaling molecule in the brain? J. Cereb. Blood Flow Metab. 35, 1069–1075.Google Scholar

  • Moskowitz, M.A., Lo, E.H., and Iadecola, C. (2010). The science of stroke: mechanisms in search of treatments. Neuron 67, 181–198.Google Scholar

  • Nagase, M., Takahashi, Y., Watabe, A.M., Kubo, Y., and Kato, F. (2014). On-site energy supply at synapses through monocarboxylate transporters maintains excitatory synaptic transmission. J. Neurosci. 34, 2605–2617.Google Scholar

  • Nedergaard, M., Goldman, S.A., Desai, S., and Pulsinelli, W.A. (1991). Acid-induced death in neurons and glia. J. Neurosci. 11, 2489–2497.Google Scholar

  • Nilsson, G.E. (1996). Brain and body oxygen requirements of Gnathonemus petersii, a fish with an exceptionally large brain. J. Exp. Biol. 199, 603–607.Google Scholar

  • Obara, M., Szeliga, M., and Albrecht, J. (2008). Regulation of pH in the mammalian central nervous system under normal and pathological conditions: fact and hypothesis. Neurochem. Int. 52, 905–919.Google Scholar

  • Pathak, D., Shields, L.Y., Mendelsohn, B.A., Haddad, D., Lin, W., Gerencser, A.A., Kim, H., Brand, M.D., Edwards, R.H., and Nakamura, K. (2015). The role of mitochondrially derived ATP in synaptic vesicle recycling. J. Biol. Chem. 290, 22325–22336.Google Scholar

  • Pekun, T.G., Lemeshchenko, V.V., Lyskova, T.I., Waseem, T.V., and Fedorovich, S.V. (2013). Influence of intra- and extracellular acidification on free radical formation and mitochondria potential in rat brain synaptosomes. J. Mol. Neurosci. 49, 211–222.Google Scholar

  • Pellerin, L. and Magistretti, P.J. (2012). Sweet sixteen for ANLS. J. Cereb. Blood Flow Metab. 32, 1152–1166.Google Scholar

  • Popova, I., Malkov, A., Ivanov, A.I., Samokhina, E., Buldakova, S., Gubkina, O., Osypov, A., Muhammadiev, R.S., Zilberter, T., Molchanov, M., et al. (2017). Metabolic correction by pyruvate halts acquired epilepsy in multiple rodent models. Neurobiol. Dis. 106, 244–254.Google Scholar

  • Rangaraju, V., Calloway, N., and Ryan, T.A. (2014). Activity-driven local ATP synthesis is required for synaptic function. Cell 156, 825–835.Google Scholar

  • Reynolds, I.J. and Hastings, T.G. (1995). Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation, J. Neurosci. 15, 3318–3327.Google Scholar

  • Rolleston, F.S. and Newsholme, E.A. (1967). Effects of fatty acids, ketone bodies, lactate and pyruvate on glucose utilization by guinea-pig cerebral cortex slices. Biochem. J. 104, 519–523.Google Scholar

  • Sampath, A., Kossoff, E.H., Furth, S.L., Pyzik, P.L., and Vining, E.P. (2007). Kidney stones and ketogenic diet: risk factors and prevention. J. Child Neurol. 22, 375–378.Google Scholar

  • Schweining, C.J. and Willoughby, D. (2002). Depolarization-induced pH microdomains and their relationship to calcium transients in isolated snail neurons. J. Physiol. 538, 371–382.Google Scholar

  • Shimazu, T., Hirshey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., et al. (2013). Supression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211–214.Google Scholar

  • Spires-Jones, T.L. and Hyman, B.T. (2014). The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 82, 756–771.Google Scholar

  • Stafstrom, C.E. and Rho, J.M. (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front. Pharmacol. 3, 59.Google Scholar

  • Südhof, T.C. (2004). The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509–547.Google Scholar

  • Südhof, T.C. (2013). Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron 80, 675–690.Google Scholar

  • Suh, S.W., Hamby, A.M., and Swanson, R.A. (2007a). Hypoglycemia, brain energetic, and hypoglycemic neuronal death. Glia 55, 1280–1286.Google Scholar

  • Suh, S.W., Gum, E.T., Hamby, A.M., Chan, P.H., and Swanson, R.A. (2007b). Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J. Clin. Invest. 117, 910–918.Google Scholar

  • Swerdlow, R.H. (2014). Bioenergetic medicine. Br. J. Pharmacol. 171, 1854–1869.Google Scholar

  • Tarasenko, A.S., Linetska, M.V., Storchak, L.G., and Himmelreich, N.H. (2006). Effectiveness of extracellular lactate/pyruvate for sustaining synaptic vesicle proton gradient generation and vesicular accumulation of GABA. J. Neurochem. 99, 787–796.Google Scholar

  • Tarasenko, A., Krupko, O., and Himmelreich, N. (2012). Reactive oxygen species induced by presynaptic glutamate receptor activation is involved in [3H]GABA release from rat brain cortical nerve terminals. Neurochem. Int. 61, 1044–1051.Google Scholar

  • Terry, R.D., Masliah, E., Salmon, D.P., Butters, N., DeTeresa, R., Hill, R., Hansen, L.A., and Katzman, R. (1991). Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580.Google Scholar

  • Tretter, L. and Adam-Vizi, V. (2004). Generation of reactive oxygen species in the reaction catalyzed by α-ketoglutarate dehydrogenase. J. Neurosci. 24, 7771–7778.Google Scholar

  • Tretter, L., Liktor, B., and Adam-Vizi, V. (2005). Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase. Neurochem. Res. 30, 1331–1338.Google Scholar

  • Tromba, C., Salvaggio, A., Racagni, G., and Volterra, A. (1992). Hypoglycemia-activated K+ channels in hippocampal neurons. Neurosci. Lett. 143, 185–189.Google Scholar

  • van der Bliek, A.M. and Meyerowitz, E.M. (1991). Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 411–414.Google Scholar

  • van Hall, G., Stromstad, M., Rasmussen, P., Jans, O., Zaar, M., Gam, C., Quistorff, B., Secher, N.H., and Nielsen, H.B. (2009). Blood lactate is an important energy source for the human brain. J. Cereb. Blood Flow Metab. 29, 1121–1129.Google Scholar

  • Velisek, L., Veliskova, J., Chudomel, O., Poon, K.-L., Robeson, K., Marshall, B., Sharma, A., and Moshe, S.L. (2008). Metabolic environment in substantia nigra reticulate is critical for the expression and control of hypoglycemia-induced seizures. J. Neurosci. 28, 9349–9362.Google Scholar

  • Wakade, C., Chong, R., Bradley, E., Thomas, B., and Morgan, J. (2014). Upregulation of GPR109A in Parkinson’s disease. PLoS One 9, e109818.Google Scholar

  • Wei, W.C., Jacobs, B., Becker, E.B., and Glitsch, M.D. (2015). Reciprocal regulation of two G protein-coupled receptors sensing extracellular concentrations of Ca2+ and H+. Proc. Natl. Acad. Sci. USA 112, 10738–10743.Google Scholar

  • Wemmie, J.A., Taugher, R.J., and Kreple, C.J. (2013). Acid-sensing ion channels in pain and disease. Nat. Rev. Neurosci. 14, 461–471.Google Scholar

  • White, H. and Venkatesh, B. (2011). Clinical review: ketones and brain injury. Crit. Care 15, 219.Google Scholar

  • Wieloch, T. (1985). Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonists. Science 230, 681–683.Google Scholar

  • Xiang, Z. and Bergold, P.J. (2000). Synaptic depression and neuronal loss in transiently acidic hippocampal slice cultures. Brain Res. 881, 77–87.Google Scholar

  • Xiong, Z.-G., Zhu, X.-M., Minami, M., Hey, J., Wei, W.-L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J., and Simon, R.P. (2004). Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118, 687–698.Google Scholar

  • Zilberter, Y., Gubkina, O., and Ivanov, A.I. (2015). A unique array of neuroprotective effects of pyruvate in neuropathology. Front. Neurosci. 9, 17.Google Scholar

About the article

Received: 2017-10-30

Accepted: 2018-03-16

Published Online: 2018-05-16

Published in Print: 2018-11-27


Citation Information: Reviews in the Neurosciences, Volume 29, Issue 8, Pages 825–835, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2017-0090.

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