Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-m9kch Total loading time: 0 Render date: 2024-05-22T02:18:22.659Z Has data issue: false hasContentIssue false

8 - Glial cell biology

from Section 1 - Making of the brain

Published online by Cambridge University Press:  01 March 2011

Hugo Lagercrantz
Affiliation:
Karolinska Institutet, Stockholm
M. A. Hanson
Affiliation:
Southampton General Hospital
Laura R. Ment
Affiliation:
Yale University, Connecticut
Donald M. Peebles
Affiliation:
University College London
Get access

Summary

Neuronal–glial interaction in nutrition and amino-acid-mediated neurotransmission

Nutrition

The main substrate for brain energy metabolism is glucose, and in the adult human brain the glucose consumption, termed cerebral metabolic rate for glucose (CMRgluc), is around 20 µmol/h per g wet weight (Sokoloff,1960). Alternative substrates may, however, be used and in this regard ketone bodies may have an important role particularly in the infant brain. The unique anatomical location of astrocytes, that is with their end-feet closely apposed to the capillaries (Fig. 8.1), has led to the proposal (Pellerin & Magistretti, 1994; Magistretti & Pellerin, 1996) that astrocytes may be the major site for uptake of glucose in the brain. As glucose will be rapidly converted into glucose 6-phosphate, which cannot cross the cell membrane, it is likely that metabolism of glucose proceeds to form lactate, which may subsequently be transferred from the astrocytes to the neurons via the monocarboxylic acid transporters present in the membranes of both types of brain cell (Fig. 8.1) and possibly most prevalent in neurons (Pellerin et al., 1998). The lactate concentration is augmented in the brain subsequent to stimulation; however, evidence for a subsequent net oxidation in the adjacent neurons is lacking (Hertz et al., 2007). Interestingly, as determined by microdialysis, astrocytes and neurons oxidize 50% each of the interstitial lactate in freely moving rats (Zielke et al., 2007).

Type
Chapter
Information
The Newborn Brain
Neuroscience and Clinical Applications
, pp. 121 - 128
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bak, L. K., Schousboe, A., Sonnewald, U., et al. (2006). Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. Journal of Cerebral Blood Flow Metabolism, 26, 1285–97.CrossRefGoogle ScholarPubMed
Benveniste, H., Drejer, J., Schousboe, A., et al. (1984). Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. Journal of Neurochemistry, 43, 1369–74.CrossRefGoogle ScholarPubMed
Bolvig, T., Larsson, O. M., Pickering, D. S., et al. (1999). Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity. European Journal of Pharmacology, 375, 367–74.CrossRefGoogle ScholarPubMed
Borden, L. A. (1996). GABA transporter heterogeneity: pharmacology and cellular localization. Neurochemistry International, 29, 335–56.CrossRefGoogle ScholarPubMed
Brown, A. M., Sickmann, H. M., Fosgerau, K., et al. (2005). Astrocyte glycogen metabolism is required for neural activity during aglycaemia or intense stimulation in mouse white matterJournal of Neuroscience Research, 79, 64–80.CrossRefGoogle ScholarPubMed
Cesar, M. & Hamprecht, B. (1995). Immunocytochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase. Journal of Neurochemistry, 64, 2312–18.CrossRefGoogle ScholarPubMed
Choi, D. W. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron, 1, 623–34.CrossRefGoogle ScholarPubMed
Clausen, R. P., Madsen, K., Larsson, O. M., et al. (2006). Structure-activity relationship and pharmacology of γ-aminobutyric acid (GABA) transport inhibitors. Advances in Pharmacology, 54, 265–84.CrossRefGoogle ScholarPubMed
Danbolt, N. C. (1994). The high-affinity uptake system for excitatory amino acids in the brain. Progress in Neurobiology, 44, 377–96.CrossRefGoogle Scholar
Danbolt, N. C. (2001). Glutamate uptake. Progress in Neurobiology, 65, 1–105.CrossRefGoogle ScholarPubMed
Dienel, G. A., Ball, K. K., & Cruz, N. F. (2007). A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover. Journal of Neurochemistry, 102, 466–78.CrossRefGoogle ScholarPubMed
Drejer, J., Meier, E., & Schousboe, A. (1983). Novel neuron-related regulatory mechanisms for astrocytic glutamate and GABA high affinity uptake. Neuroscience Letters, 37, 301–6.CrossRefGoogle ScholarPubMed
Drejer, J., Larsson, O. M., Kvamme, E., et al. (1985). Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo. Neurochemical Research, 10, 49–62.CrossRefGoogle ScholarPubMed
Dringen, R., Gebhardt, R., & Hamprecht, B. (1993). Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Research, 623, 208–14.CrossRefGoogle ScholarPubMed
Gegelashvili, G. & Schousboe, A. (1997). High-affinity glutamate transporters: regulation of expression and activity. Molecular Pharmacology, 52, 6–15.CrossRefGoogle ScholarPubMed
Gegelashvili, G., Civenni, G., Racagni, G., et al. (1996). Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. Neuroreport, 8, 261–5.CrossRefGoogle ScholarPubMed
Gegelashvili, G., Danbolt, N. C., & Schousboe, A. (1997). Neuronal soluble factors differentially regulate the expression of the GLT1 and GLAST glutamate transporters in cultured astroglia. Journal of Neurochemistry, 69, 2612–15.CrossRefGoogle ScholarPubMed
Gram, L., Larsson, O. M., Johnsen, A. H., et al. (1988). Effects of valproate, vigabatrin and aminooxyacetic acid on release of endogenous and exogenous GABA from cultured neurons. Epilepsy Research, 2, 87–95.CrossRefGoogle ScholarPubMed
Hertz, L. (1979). Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Progress in Neurobiology, 13, 277–323.CrossRefGoogle ScholarPubMed
Hertz, L. & Schousboe, A. (1987). Primary cultures of GABAergic and glutamatergic neurons as model systems to study neurotransmitter functions. I. Differentiated cells. In Model Systems of Development and Aging of the Nervous System, eds. Vernadakis, A., Privat, A., Lauder, J. M., et al. Boston, MA: M. Nijhoff, pp. 19–31.CrossRefGoogle Scholar
Hertz, L., Bock, E., & Schousboe, A. (1978). GFA content, glutamate uptake and activity of glutamate metabolizing enzymes in differentiating mouse astrocytes in primary cultures. Developmental Neuroscience, 1, 226–38.Google Scholar
Hertz, L., Peng, L., Westergaard, N., et al. (1992). Neuronal-astrocytic interactions in metabolism of transmitter amino acids of the glutamate family. In Alfred Benzon Symposium 32, Drug Research Related to Neuroactive Amino Acids, eds. Schousboe, A., Diemer, N. H., & Kofod, H.. Copenhagen: Munksgaard, pp. 30–48.Google Scholar
Hertz, L., Peng, L., & Dienel, G. A. (2007). Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. Journal of Cerebral Blood Flow and Metabolism, 27, 219–49.CrossRefGoogle ScholarPubMed
Kettenmann, H. & Ransom, B. R., eds. (1995). Neuroglia. Oxford: Oxford University Press.Google Scholar
Kurz, G. M., Wiesinger, H., & Hamprecht, B. (1993). Purification of cytosolic malic enzyme from bovine brain, generation of monoclonal antibodies, and immunocytochemical localization of the enzyme in glial cells of neural primary cultures. Journal of Neurochemistry, 60, 1467–74.CrossRefGoogle ScholarPubMed
Larsson, O. M. & Schousboe, A. (1981). Comparison between (RS)-nipecotic acid and GABA transport in cultured astrocytes: coupling with two sodium ions. Neurochemical Research, 6, 257–66.CrossRefGoogle ScholarPubMed
Larsson, O. M., Drejer, J., Hertz, L., et al. (1983). Ion dependency of uptake and release of GABA and (RS)-nipecotic acid studies in cultured mouse brain cortex neurons. Journal of Neuroscience Research, 9, 291–303.CrossRefGoogle Scholar
Larsson, O. M., Drejer, J., Kvamme, E., et al. (1985). Ontogenetic development of glutamate and GABA metabolising enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo. International Journal of Developmental Neuroscience, 3, 177–85.CrossRefGoogle Scholar
Lehre, K. P. & Danbolt, N. C. (1998). The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. Journal of Neuroscience, 18, 8751–7.CrossRefGoogle ScholarPubMed
Levy, L. M., Lehre, K. P., Walaas, S. I., et al. (1995). Down-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain. European Journal of Neuroscience, 7, 2036–41.CrossRefGoogle ScholarPubMed
Levy, L. M., Warr, O., & Attwell, D. (1998). Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. Journal of Neuroscience, 18, 9620–8.CrossRefGoogle Scholar
Lodge, D. (1997). Subtypes of glutamate receptors. In The Ionotropic Glutamate Receptors, eds. Monaghan, D. T. & Wenthold, R. J.. New Jersey: Humana Press, pp. 1–38.Google Scholar
Lovatt, D., Sonnewald, U., Waagepetersen, H. S., et al. (2007). The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. Journal of Neuroscience, 47, 12255–66.CrossRefGoogle Scholar
Madsen, K. B., Larsson, O. M., & Schousboe, A. (2008). Regulation of excitation by GABA neurotransmission: focus on metabolism and transport. Results and Problems in Cell Differentiation, 44, 201–21.CrossRefGoogle ScholarPubMed
Magistretti, P. J. & Pellerin, L. (1996). The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Molecular Psychiatry, 1, 445–52.Google ScholarPubMed
Martin, D. L. (1976). Carrier-mediated transport and removal of GABA from synaptic regions. In GABA in Nervous System function, eds. Roberts, E., Chase, T. N., & Tower, D. B.. New York: Raven Press, pp. 347–86.Google Scholar
McCarthy, A. D. & Tipton, K. F. (1983). Glutamate dehydrogenase. In Glutamine, Glutamate and GABA in the Central Nervous System, eds. Hertz, L., Kvamme, E., McGeer, E. G., et al. New York: Alan R. Liss, pp. 19–32.Google Scholar
McKenna, M. C., Sonnewald, U., Huang, X., et al. (1996). Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. Journal of Neurochemistry, 66, 386–93.CrossRefGoogle ScholarPubMed
Meier, E., Hertz, L., & Schousboe, A. (1991). Neurotransmitters as developmental signals. Neurochemistry International, 19, 1–15.CrossRefGoogle Scholar
Nicholls, D. & Attwell, D. (1990). The release and uptake of excitatory amino acids. Trends in Pharmacological Sciences, 11, 462–8.CrossRefGoogle ScholarPubMed
Nissen, J., Schousboe, A., Halkier, T., et al. (1992). Purification and characterization of an astrocyte GABA-carrier inducing protein (GABA-CIP) released from cerebellar granule cells. Glia, 6, 236–43.CrossRefGoogle ScholarPubMed
Norenberg, M. D. & Martinez-Hernandez, A. (1979). Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Research, 161, 303–10.CrossRefGoogle ScholarPubMed
Pellerin, L. & Magistretti, P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proceedings of the National Academy of Sciences of the U S A, 15, 10625–9.CrossRefGoogle Scholar
Pellerin, L., Pellegri, G., Bittar, P. G., et al. (1998). Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Developmental Neuroscience, 20, 291–9.CrossRefGoogle ScholarPubMed
Plaitakis, A. (1990). Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis: a hypothesis. Annals of Neurology, 28, 3–8.CrossRefGoogle ScholarPubMed
Roberts, E. (1991). Living systems are tonically inhibited, autonomous optimizers, and disinhibition coupled to variability generation is their major organizing principle: inhibitory command-control at levels of membrane, genome, metabolism, brain, and society. Neurochemical Research, 16, 409–21.CrossRefGoogle ScholarPubMed
Rothe, F., Brosz, M., & Storm-Mathisen, J. (1994). Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex. Neuroscience, 62, 1133–46.CrossRefGoogle ScholarPubMed
Rothstein, J. D., Martin, L. J., & Kuncl, R. W. (1992). Decreased brain and spinal cord glutamate transport in amyotrophic lateral sclerosis. New England Journal of Medicine, 326, 1464–8.CrossRefGoogle ScholarPubMed
Rothstein, J. D., Jin, L., Dykes-Hoberg, M., et al. (1993). Chronic glutamate uptake inhibition produces a model of slow neurotoxicity. Proceedings of the National Academy of Sciences of the U S A, 90, 6591–5.CrossRefGoogle ScholarPubMed
Schoepp, D. D. & Conn, P. J. (1993). Metabotropic glutamate receptors in brain function and pathology. Trends in Pharmacological Sciences, 14, 13–20.CrossRefGoogle ScholarPubMed
Schousboe, A. (1981). Transport and metabolism of glutamate and GABA in neurons and glial cells. International Review of Neurobiology, 22, 1–45.CrossRefGoogle ScholarPubMed
Schousboe, A. (1990). Neurochemical alterations associated with epilepsy or seizure activity. In Comprehensive Epileptology, Dam, M. & Gram, L., eds. New York: Raven Press, pp. 1–16.Google Scholar
Schousboe, A. & Frandsen, A. (1995). Glutamate receptors and neurotoxicity. In CNS Neurotransmitters and Neuromodulators: Glutamate, ed. Stone, T. W.. Raton, Boca, FL: CRC Press, pp. 239–51.Google Scholar
Schousboe, A. & Waagepetersen, H. S. (2005). Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotoxicity Research, 8, 221–5.CrossRefGoogle ScholarPubMed
Schousboe, A., Lisy, V., & Hertz, L. (1976). Postnatal alterations in effects of potassium on uptake and release of glutamate and GABA in rat brain cortex slices. Journal of Neurochemistry, 26, 1023–7.CrossRefGoogle ScholarPubMed
Schousboe, A., Hertz, L., & Svenneby, G. (1977a). Uptake and metabolism of GABA in astrocytes cultured from dissociated mouse brain hemispheres. Neurochemical Research, 2, 217–29.CrossRefGoogle ScholarPubMed
Schousboe, A., Svenneby, G., & Hertz, L. (1977b). Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres. Journal of Neurochemistry, 29, 999–1005.CrossRefGoogle ScholarPubMed
Schousboe, A., Drejer, J., & Hertz, L. (1988). Uptake and release of glutamate and glutamine in neurons and astrocytes in primary cultures. In Glutamine and Glutamate in Mammals, Vol. II, ed. Kvamme, E.. Raton, Boca, FL: CRC Press, pp. 21–38.Google Scholar
Schousboe, A., Sarup, A., Larsson, O. M., et al. (2004). GABA transporters as drug targets for modulation of GABAergic activity. Biochemical Pharmacology, 68, 1557–63.CrossRefGoogle ScholarPubMed
Shank, R. P., Bennett, G. S., Freytag, S. O., et al. (1985). Pyruvate carboxylase: astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Research, 329, 364–7.CrossRefGoogle ScholarPubMed
Shulman, R. G., Hyder, F., & Rothman, D. L. (2001). Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proceedings of the National Academy of Sciences of the U S A, 98, 6417–22.CrossRefGoogle ScholarPubMed
Sickmann, H. M., Schousboe, A., Fosgerau, K, et al. (2005). Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes. Neurochemical Research, 30, 1295–304.CrossRefGoogle ScholarPubMed
Sokoloff, L. (1960). The metabolism of the central nervous system in vivo. In Handbook of Physiology – Neurophysiology, Vol. 3, eds. Magoun, H. W. & Hall, V. E.. Washington, DC: American Physiological Society, pp. 1843–64.Google Scholar
Sonnewald, U., Westergaard, N., Petersen, S. B., et al. (1993). Metabolism of [U-13C]glutamate in astrocytes studied by 13C NMR spectroscopy: incorporation of more label into lactate than into glutamine demonstrates the importance of the TCA cycle. Journal of Neurochemistry, 61, 1179–82.CrossRefGoogle Scholar
Sonnewald, U., Westergaard, N., & Schousboe, A. (1997). Glutamate transport and metabolism in astrocytes. Glia, 21, 56–63.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Waagepetersen, H. S., Bakken, I. J., Larsson, O. M., et al. (1998a). Metabolism of lactate in cultured GABAergic neurons studied by 13C-NMR spectroscopy. Journal of Cerebral Blood Flow Metabolism, 18, 109–17.CrossRefGoogle Scholar
Waagepetersen, H. S., Bakken, I. J., Larsson, O. M., et al. (1998b). Comparison of lactate and glucose metabolism in cultured neocortical neurons and astrocytes using 13C NMR spectroscopy. Developmental Neuroscience, 20, 310–20.CrossRefGoogle ScholarPubMed
Waagepetersen, H. S., Sonnewald, U., & Schousboe, A. (1999). The GABA paradox: multiple roles as metabolite, neurotransmitter, and neurodifferentiative agent. Journal of Neurochemistry, 73, 1335–42.CrossRefGoogle ScholarPubMed
Waagepetersen, H. S., Qu, H., Sonnewald, U., et al. (2005). Role of glutamine and neuronal glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic neurons. Neurochemistry International, 47, 92–102.CrossRefGoogle ScholarPubMed
Westergaard, N., Sonnewald, U., & Schousboe, A. (1995). Metabolic trafficking between neurons and astrocytes: the glutamate/glutamine cycle revisited. Developmental Neuroscience, 17, 203–11.CrossRefGoogle ScholarPubMed
Westergaard, N., Drejer, J., Schousboe, A., et al. (1996). Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C]glutamate. Glia, 17, 160–8.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
White, H. S., Watson, W. P., Hansen, S., et al. (2005). First demonstration of a functional role for CNS betaine/GABA transporter (mGAT2) based on synergistic anticonvulsant action among inhibitors of mGAT1 and mGAT2. Journal of Pharmacology and Experimental Therapeutics, 312, 866–74.CrossRefGoogle Scholar
Wu, D. K., Scully, S., & Vellis, J. (1988). Induction of glutamine synthetase in rat astrocytes by co-cultivation with embryonic chick neurons. Journal of Neurochemistry, 50, 929–35.CrossRefGoogle ScholarPubMed
Yu, A. C., Schousboe, A., & Hertz, L. (1982). Metabolic fate of [14C]-labelled glutamate in astrocytes in primary cultures. Journal of Neurochemistry, 39, 954–60.CrossRefGoogle Scholar
Yu, A. C. H., Drejer, J., Hertz, L., et al. (1983). Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. Journal of Neurochemistry, 41, 1484–7.CrossRefGoogle ScholarPubMed
Zielke, H. R., Zielke, C. L., Baab, P. J., et al. (2007). Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. Journal of Neurochemistry, 101, 9–16.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×