Skip to content

Neuroscience

Frontiers in Neuroenergetics ·

Volume 3 - 2011 | https://doi.org/10.3389/fnene.2011.00002

Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices

  • Anton Ivanov1
  • Marat Mukhtarov1
  • Piotr Bregestovski1
  • Yuri Zilberter1
  1. 1 Faculté de Médecine Timone, Institut National de la Santé et de la Recherche Médicale U751, Université de la Méditerranée Marseille, France
Article metrics0 viewsView details

Abstract

Although numerous experimental data indicate that lactate is efficiently used for energy by the mature brain, the direct measurements of energy metabolism parameters during neuronal network activity in early postnatal development have not been performed. Therefore, the role of lactate in the energy metabolism of neurons at this age remains unclear. In this study, we monitored field potentials and contents of oxygen and NAD(P)H in correlation with oxidative metabolism during intense network activity in the CA1 hippocampal region of neonatal brain slices. We show that in the presence of glucose, lactate is effectively utilized as an energy substrate, causing an augmentation of oxidative metabolism. Moreover, in the absence of glucose lactate is fully capable of maintaining synaptic function. Therefore, during network activity in neonatal slices, lactate can be an efficient energy substrate capable of sustaining and enhancing aerobic energy metabolism.

Keywords

References

  1. Abi-Saab W. M., Maggs D. G., Jones T., Jacob R., Srihari V., Thompson J., Kerr D., Leone P., Krystal J. H., Spencer D. D., During M. J., Sherwin R. S. (2002). Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J. Cereb. Blood Flow Metab. 22, 271 – 279. doi:10.1097/00004647-200203000-00004
  2. Barros L. F., Deitmer J. W. (2010). Glucose and lactate supply to the synapse. Brain Res. Rev. 63, 149 – 159.
  3. Ben-Ari Y., Gaiarsa J. L., Tyzio R., Khazipov R. (2007). GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol. Rev. 87, 1215 – 1284.
  4. Bevensee M. O., Cummins T. R., Haddad G. G., Boron W. F., Boyarsky G. (1996). pH regulation in single CA1 neurons acutely isolated from the hippocampi of immature and mature rats. J. Physiol. 494 (Pt 2), 315 – 328.
  5. Boumezbeur F., Petersen K. F., Cline G. W., Mason G. F., Behar K. L., Shulman G. I., Rothman D. L. (2010). The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J. Neurosci. 30, 13983 – 13991. doi:10.1523/jneurosci.2040-10.2010
  6. Brennan A. M., Connor J. A., Shuttleworth C. W. (2006). NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function. J. Cereb. Blood Flow Metab. 26, 1389 – 1406. doi:10.1038/sj.jcbfm.9600292
  7. Brennan A. M., Connor J. A., Shuttleworth C. W. (2007). Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation. J. Neurosci. Res. 85, 3233 – 3243.
  8. Cavus I., Kasoff W. S., Cassaday M. P., Jacob R., Gueorguieva R., Sherwin R. S., Krystal J. H., Spencer D. D., Abi-Saab W. M. (2005). Extracellular metabolites in the cortex and hippocampus of epileptic patients. Ann. Neurol. 57, 226 – 235.
  9. Cherubini E., Ben-Ari Y., Krnjevic K. (1989). Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus. J. Neurophysiol. 62, 882 – 895.
  10. Dora E., Gyulai L., Kovach A. G. (1984). Determinants of brain activation-induced cortical NAD/NADH responses in vivo. Brain Res. 299, 61 – 72. doi:10.1016/0006-8993(84)90788-1
  11. Erecinska M., Cherian S., Silver I. A. (2004). Energy metabolism in mammalian brain during development. Prog. Neurobiol. 73, 397 – 445.
  12. Fukao T., Lopaschuk G. D., Mitchell G. A. (2004). Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. Prostaglandins Leukot. Essent. Fatty Acids 70, 243 – 251. doi:10.1016/j.plefa.2003.11.001
  13. Galeffi F., Foster K. A., Sadgrove M. P., Beaver C. J., Turner D. A. (2007). Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices. J. Neurochem. 103, 2449 – 2461. doi:10.1111/j.1471-4159.2007.04939.x
  14. Galeffi F., Somjen G. G., Foster K. A., Turner D. A. (2011). Simultaneous monitoring of tissue PO(2) and NADH fluorescence during synaptic stimulation and spreading depression reveals a transient dissociation between oxygen utilization and mitochondrial redox state in rat hippocampal slices. J. Cereb. Blood Flow Metab. 31, 626 – 639. doi:10.1038/jcbfm.2010.136
  15. Gallagher C. N., Carpenter K. L., Grice P., Howe D. J., Mason A., Timofeev I., Menon D. K., Kirkpatrick P. J., Pickard J. D., Sutherland G. R., Hutchinson P. J. (2009). The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain 132, 2839 – 2849. doi:10.1093/brain/awp202
  16. Garcia A. J. III, Putnam R. W., Dean J. B. (2010). Hyperbaric hyperoxia and normobaric reoxygenation increase excitability and activate oxygen-induced potentiation in CA1 hippocampal neurons. J. Appl. Physiol. 109, 804 – 819.
  17. Haddad G. G., Donnelly D. F. (1990). O2 deprivation induces a major depolarization in brain stem neurons in the adult but not in the neonatal rat. J. Physiol. 429, 411 – 428.
  18. Hajos N., Ellender T. J., Zemankovics R., Mann E. O., Exley R., Cragg S. J., Freund T. F., Paulsen O. (2009). Maintaining network activity in submerged hippocampal slices: importance of oxygen supply. Eur. J. Neurosci. 29, 319 – 327.
  19. Holmgren C. D., Mukhtarov M., Malkov A. E., Popova I. Y., Bregestovski P., 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. doi:10.1111/j.1471-4159.2009.06506.x
  20. Juge N., Gray J. A., Omote H., Miyaji T., Inoue T., Hara C., Uneyama H., Edwards R. H., Nicoll R. A., Moriyama Y. (2010). Metabolic control of vesicular glutamate transport and release. Neuron 68, 99 – 112. doi:10.1016/j.neuron.2010.09.002
  21. Kasischke K. A., Vishwasrao H. D., Fisher P. J., Zipfel W. R., Webb W. W. (2004). Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305, 99 – 103. doi:10.1126/science.1096485
  22. Kass I. S., Lipton P. (1989). Protection of hippocampal slices from young rats against anoxic transmission damage is due to better maintenance of ATP. J. Physiol. 413, 1 – 11.
  23. Kirmse K., Witte O. W., Holthoff K. (2010). GABA depolarizes immature neocortical neurons in the presence of the ketone body β-hydroxybutyrate. J. Neurosci. 30, 16002 – 16007. doi:10.1523/JNEUROSCI.2534-10.2010
  24. Klaidman L. K., Leung A. C., Adams J. D. Jr. (1995). High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions. Anal. Biochem. 228, 312 – 317.
  25. Langemann H., Alessandri B., Mendelowitsch A., Feuerstein T., Landolt H., Gratzl O. (2001). Extracellular levels of glucose and lactate measured by quantitative microdialysis in the human brain. Neurol. Res. 23, 531 – 536.
  26. Lehninger A. L. (2005). “Principles of metabolic regulation: glucose and glycogen,” in Principles of biochemistry, 4th edn, eds Nelson D. L., Cox M. M. (Boston, MA: W. H. Freeman), 560 – 600.
  27. Levasseur J. E., Alessandri B., Reinert M., Clausen T., Zhou Z., Altememi N., Bullock M. R. (2006). Lactate, not glucose, up-regulates mitochondrial oxygen consumption both in sham and lateral fluid percussed rat brains. Neurosurgery 59, 1122 – 1130. [Discussion 1130–1121].
  28. Lewis D. V., Schuette W. H. (1976). NADH fluorescence, [K+]0 and oxygen consumption in cat cerebral cortex during direct cortical stimulation. Brain Res. 110, 523 – 535. doi:10.1016/0006-8993(76)90863-5
  29. Lipton P. (1973). Effects of membrane depolarization on nicotinamide nucleotide fluorescence in brain slices. Biochem. J. 136, 999 – 1009.
  30. Lothman E., Lamanna J., Cordingley G., Rosenthal M., Somjen G. (1975). Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res. 88, 15 – 36. doi:10.1016/0006-8993(75)90943-9
  31. Maddock R. J., Buonocore M. H., Lavoie S. P., Copeland L. E., Kile S. J., Richards A. L., Ryan J. M. (2006). Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla. Psychiatry Res. 148, 47 – 54. doi:10.1016/j.pscychresns.2006.02.004
  32. Magistretti P. J. (2009). Role of glutamate in neuron-glia metabolic coupling. Am. J. Clin. Nutr. 90, 875S – 880S.
  33. Mangia S., Garreffa G., Bianciardi M., Giove F., Di Salle F., Maraviglia B. (2003). The aerobic brain: lactate decrease at the onset of neural activity. Neuroscience 118, 7 – 10. doi:10.1016/S0306-4522(02)00792-3
  34. Mangia S., Giove F., Tkac I., Logothetis N. K., Henry P. G., Olman C. A., Maraviglia B., Di Salle F., Ugurbil K. (2009). Metabolic and hemodynamic events after changes in neuronal activity: current hypotheses, theoretical predictions and in vivo NMR experimental findings. J. Cereb. Blood Flow Metab. 29, 441 – 463. doi:10.1038/jcbfm.2008.134
  35. Mayevsky A., Chance B. (2007). Oxidation-reduction states of NADH in vivo: from animals to clinical use. Mitochondrion 7, 330 – 339. doi:10.1016/j.mito.2007.05.001
  36. McNay E. C., Sherwin R. S. (2004). From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose measurements. J. Neurosci. Methods 132, 35 – 43.
  37. Medina J. M., Tabernero A. (2005). Lactate utilization by brain cells and its role in CNS development. J. Neurosci. Res. 79, 2 – 10.
  38. Mukhtarov M., Ivanov A., Zilberter Y., Bregestovski P. (2011). Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification. J. Neurochem. 116, 316 – 321. doi:10.1111/j.1471-4159.2010.07111.x
  39. Nabetani M., Okada Y., Kawai S., Nakamura H. (1995). Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats. Int. J. Dev. Neurosci. 13, 3 – 12.
  40. Nehlig A. (2004). Brain uptake and metabolism of ketone bodies in animal models. Prostaglandins Leukot. Essent. Fatty Acids 70, 265 – 275. doi:10.1016/j.plefa.2003.07.006
  41. Pellerin L., Bouzier-Sore A. K., Aubert A., Serres S., Merle M., Costalat R., Magistretti P. J. (2007). Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55, 1251 – 1262. doi:10.1002/glia.20528
  42. Pellerin L., Magistretti P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U.S.A. 91, 10625 – 10629.
  43. Prins M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. J. Cereb. Blood Flow Metab. 28, 1 – 16. doi:10.1038/sj.jcbfm.9600543
  44. Rosenthal M., Jobsis F. F. (1971). Intracellular redox changes in functioning cerebral cortex. II. Effects of direct cortical stimulation. J. Neurophysiol. 34, 750 – 762.
  45. Ruusuvuori E., Kirilkin I., Pandya N., Kaila K. (2010). Spontaneous network events driven by depolarizing GABA action in neonatal hippocampal slices are not attributable to deficient mitochondrial energy metabolism. J. Neurosci. 30, 15638 – 15642. doi:10.1523/JNEUROSCI.3355-10.2010
  46. Schousboe A., Bak L. K., Sickmann H. M., Sonnewald U., Waagepetersen H. S. (2007). Energy substrates to support glutamatergic and GABAergic synaptic function: role of glycogen, glucose and lactate. Neurotox. Res. 12, 263 – 268.
  47. Schurr A. (2006). Lactate: the ultimate cerebral oxidative energy substrate? J. Cereb. Blood Flow Metab. 26, 142 – 152. doi:10.1038/sj.jcbfm.9600174
  48. Schurr A., Miller J. J., Payne R. S., Rigor B. M. (1999). An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J. Neurosci. 19, 34 – 39.
  49. Schurr A., Payne R. S. (2007). Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro electrophysiological study. Neuroscience 147, 613 – 619. doi:10.1016/j.neuroscience.2007.05.002
  50. Schurr A., West C. A., Rigor B. M. (1988). Lactate-supported synaptic function in the rat hippocampal slice preparation. Science 240, 1326 – 1328. doi:10.1126/science.3375817
  51. Schwiening C. J., Boron W. F. (1994). Regulation of intracellular pH in pyramidal neurones from the rat hippocampus by Na(+)-dependent Cl(−)-HCO3- exchange. J. Physiol. 475, 59 – 67.
  52. Shuttleworth C. W. (2010). Use of NAD(P)H and flavoprotein autofluorescence transients to probe neuron and astrocyte responses to synaptic activation. Neurochem. Int. 56, 379 – 386.
  53. Tsai Y. C., Chou Y. C., Wu A. B., Hu C. M., Chen C. Y., Chen F. A., Lee J. A. (2006). Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes. Life Sci. 78, 1385 – 1391. doi:10.1016/j.lfs.2005.07.013
  54. Turner D. A., Foster K. A., Galeffi F., Somjen G. G. (2007). Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro. Trends Neurosci. 30, 390 – 398. doi:10.1016/j.tins.2007.06.001
  55. Tyzio R., Allene C., Nardou R., Picardo M. A., Yamamoto S., Sivakumaran S., Caiati M. D., Rheims S., Minlebaev M., Milh M., Ferre P., Khazipov R., Romette J. L., Lorquin J., Cossart R., Khalilov I., Nehlig A., Cherubini E., Ben-Ari Y. (2011). Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate. J. Neurosci. 31, 34 – 45. doi:10.1523/JNEUROSCI.3314-10.2011
  56. Wada H., Okada Y., Nabetani M., Nakamura H. (1997). The effects of lactate and beta-hydroxybutyrate on the energy metabolism and neural activity of hippocampal slices from adult and immature rat. Brain Res. Dev. Brain Res. 101, 1 – 7. doi:10.1016/S0165-3806(97)00007-2
  57. Ward Platt M., Deshpande S. (2005). Metabolic adaptation at birth. Semin. Fetal Neonatal Med. 10, 341 – 350. doi:10.1016/j.siny.2005.04.001
  58. Zielke H. R., Zielke C. L., Baab P. J. (2009). Direct measurement of oxidative metabolism in the living brain by microdialysis: a review. J. Neurochem. 109 (Suppl. 1), 24 – 29. doi:10.1111/j.1471-4159.2009.05941.x
  59. Zilberter Y., Zilberter T., Bregestovski P. (2010). Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis. Trends Pharmacol. Sci. 31, 394 – 401.

Citation

Ivanov, A., et al. (2011). Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices. Frontiers in Neuroenergetics, Volume 3. https://doi.org/
Received
Accepted
Published
Volume
3 - 2011

Copyright

Copyright © 2011 Ivanov, Mukhtarov, Bregestovski and Zilberter.

License: http://www.frontiersin.org/licenseagreement

Article metrics

Views
0
Downloads
0
Citations
0
Shares
0