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Primary astrocyte cultures—a key to astrocyte function

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Summary

  1. 1.

    Morphological studies have established the ubiquitous nature of astrocytes in the CNS. Their processes surround capillaries and synapses, form the subpial and subependymal layers, and seemingly invest every neuronal surface not covered by other neuronal surfaces or oligodendroglial membranes. Although such interrelationships have long suggested that astrocytes may play many critical roles, there still remains relatively little experimental information on the functions and properties of these cells.

  2. 2.

    About a decade ago it became evident that primary cultures from neonatal rodent brains can consist predominantly of normal astrocytes. Based on these findings there is now an increasing number of studies in which such primary cultures are being used to help unravel the continuing enigma of the properties and functions of astrocytes. Aspects of this work are reviewed in this article. Such work has already shown that astrocytes in primary culture exhibit the basic electrophysiological characteristics which had been the only functional property well established for these cellsin situ.

  3. 3.

    Further studies of the electrophysiological properties of these cells, which can be correlated with ion transport studies, are beginning to show that astrocytes may have more complex electrophysiological properties than had previously been supposed, as well as a number of important electrically silent ion fluxes. In addition, astrocytes in primary culture show uptake of and receptors for a number of transmitters, properties which have wide-ranging implications.

  4. 4.

    Studies in culture also support workin vivo that astroglia may have an important role in neuronal development.

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References

  • Banker, G. A. (1980). Trophic interactions between astroglial cells and hippocampal neurons in culture.Science 209809–810.

    Google Scholar 

  • Bock, E., Moller, M., Nissen, C., and Sensenbrenner, M. (1977). Glial fibrillary acidic protein in primary astroglial cell cultures derived from newborn rat brain.FEBS Lett. 83207–211.

    Google Scholar 

  • Booher, J., and Sensenbrenner, M. (1972). Growth and cultivation of dissociated neurons and glial cells from embryonic chick, rat and human brain in flask cultures.Neurobiology 297–105.

    Google Scholar 

  • Bowman, C. L., Edwards, C., and Kimelberg, H. K. (1983). Tetrodotoxin-sensitive depolarizations induced by veratridine andα-scorpion toxin in primary astrocytes in culture.Biophys. J. 41:386a.

    Google Scholar 

  • Delaunoy, J. P., Hog, F., Devilliers, G., Bansart, M., Mandel, P., and Sensenbrenner, M. (1980). Developmental changes and localization of carbonic anhydrase in cerebral hemispheres of the rat and in rat glial cell cultures.Cell. Mol. Biol. 26235–240.

    Google Scholar 

  • Ebersolt, C., Perez, M., and Bockaert, J. (1981a). Neuronal, glial and meningeal localizations of neurotransmitter-sensitive adenylate cyclase in cerebral cortex of mice.Brain Res. 213139–150.

    Google Scholar 

  • Ebersolt, C., Perez, M., and Bockaert, J. (1981b).α 1 andα 2 adrenergic receptors in mouse brain astrocytes from primary cultures.J. Neurosci. Res. 6643–652.

    Google Scholar 

  • Ebersolt, C., Perez, M., Vassent, G., and Bockaert, J. (1981c). Characteristics of theβ 1 andβ 2-adrenergic-sensitive adenylate cyclases in glial cell primary cultures and their comparison withβ 2-adrenergic-sensitive adenylate cyclase of meningeal cells.Brain Res. 213151–161.

    Google Scholar 

  • Fischer, G., Leutz, A., and Schachner, M. (1982). Cultivation of immature astrocytes of mouse cerebellum in a serum-free, hormonally defined medium. Appearance of the mature astrocytic phenotype after addition of serum.Neurosci. Lett. 29297–302.

    Google Scholar 

  • Ghandour, M. S., Langley, O. K., Vincendon, G., and Gombos, G. (1979). Double labeling immunohistochemical technique provides evidence of the specificity of glial cell markers.J. Histochem. Cytochem. 271634–1637.

    Google Scholar 

  • Green, A. R., and Costain, D. W. (1981).Pharmacology and Biochemistry of Psychiatric Disorders, John Wiley and Sons, New York, Toronto, pp. 71–88.

    Google Scholar 

  • Gutnick, M. J., Connors, B. W., and Ransom, B. R. (1981). Dye-coupling between glial cells in the guinea pig neocortical slice.Brain Res. 213486–492.

    Google Scholar 

  • Harden, T. K., and McCarthy, K. D. (1982). Identification of the beta adrenergic receptor subtype on astroglia purified from rat brain.J. Pharmacol. Exp. Ther. 222600–605.

    Google Scholar 

  • Hatten, M. E., and Liem, R. K. H. (1981). Astroglial cells provide a template for the positioning of developing cerebellar neuronsin vivo.J. Cell Biol. 90622–630.

    Google Scholar 

  • Hertz, L. (1978). An intense potassium uptake into astrocytes, its further enhancement by high concentrations of potassium, and its possible involvement in potassium homeostasis at the cellular level.Brain Res. 145202–208.

    Google Scholar 

  • Hertz, L. (1981). Features of astrocytic function apparently involved in the response of central nervous tissue to ischemia-hypoxia.J. Cerebr. Blood Flow Metab. 1143–153.

    Google Scholar 

  • Hertz, L. (1982). Astrocytes. InHandbook of Neurochemistry (Lajtha, A., Ed.), Plenum Press, New York, pp. 319–355.

    Google Scholar 

  • Hertz, L., Mukerji, S., and Richardson, J. S. (1981). Down-regulation ofβ-adrenergic activity in astroglia by chronic treatment with an antidepressant drug.Eur. J. Pharmacol. 72267–268.

    Google Scholar 

  • Hertz, L., Juurlink, B. J. H., Fosmark, H., and Schousboe, A. (1982). Methodological appendix: Astrocytes in primary cultures. InNeuroscience Approached Through Cell Culture, Vol. 1 (Pfeiffer, S. E., Ed.), CRC Press, Boca Raton, pp. 175–186.

    Google Scholar 

  • Hirano, A. (1981). Astrocytes. InA Guide to Neuropathology, Igaku-Shoin, New York, Tokyo, pp. 204–224.

    Google Scholar 

  • Hirata, H., Slater, N. T., and Kimelberg, H. K. (1983).α-Adrenergic receptor-mediated depolarization of rat neocortical astrocytes in primary culture.Brain Res. (in press).

  • Hökfelt, T., and Ljungdahl, A. (1971). Uptake of [3H]noradrenaline andγ-[3H]aminobutyric acid in isolated tissues of rat: An autoradiographic and fluorescence microscopic study.Prog. Brain Res. 3487–102.

    Google Scholar 

  • Hösli, L., and Hösli, E. (1978). Action and uptake of neurotransmitters in CNS tissue culture.Rev. Physiol. Biochem. Pharmacol. 81136–175.

    Google Scholar 

  • Hösli, L., Hösli, E., Zehntner, C., Lehmann, R., and Lutz, T. W. (1982). Evidence for the existence ofα-andβ-adrenoceptors on cultured glial cells—an electrophysiological study.Neuroscience 72867–2872.

    Google Scholar 

  • Kimelberg, H. K. (1981). Active accumulation and exchange transport of chloride in astroglial cells in culture.Biochim. Biophys. Acta 646179–184.

    Google Scholar 

  • Kimelberg, H. K., and Hirata, H. (1981). Electrophysiology of and sensitivity to furosemide and MK473 of C1 transport in primary astrocyte cultures.Soc. Neurosci. Abstr. 7698.

    Google Scholar 

  • Kimelberg, H. K., and Pelton, E. W. (1983). High-affinity uptake of [3H]norepinephrine by primary astrocyte cultures and its inhibition by tricyclic antidepressants.J. Neurochem. 401265–1270.

    Google Scholar 

  • Kimelberg, H. K., and Ricard, C. (1982). Control of intracellular pH in primary astrocyte cultures by external Na+.Trans. Am. Soc. Neurochem. 13112.

    Google Scholar 

  • Kimelberg, H. K., Narumi, S., and Bourke, R. S. (1978). Enzymatic and morphological properties of primary rat brain astrocyte cultures, and enzyme developmentin vivo.Brain Res. 15355–77.

    Google Scholar 

  • Kimelberg, H. K., Biddlecome, S., and Bourke, R. S. (1979a). SITS-inhibitable C1 transport and Na+-dependent H+ production in primary astroglial cultures.Brain Res. 173111–124.

    Google Scholar 

  • Kimelberg, H. K., Bowman, C., Biddlecome, S., and Bourke, R. S. (1979b). Cation transport and membrane potential properties of primary astroglial cultures from neonatal rat brains.Brain Res. 177533–550.

    Google Scholar 

  • Kimelberg, H. K., Hirata, H., Bowman, C., and Mazurkiewicz, J. (1982a). Effects of K+, Na+ and C1 on membrane potentials and I-V curves of primary astrocyte cultures.Soc. Neurosci. Abstr. 8238.

    Google Scholar 

  • Kimelberg, H. K., Stieg, P. E., and Mazurkiewicz, J. E. (1982b). Immunocytochemical and biochemical analysis of carbonic anhydrase in primary astrocyte cultures from rat brain.J. Neurochem. 39734–742.

    Google Scholar 

  • Kuffler, S. W. (1967). Neuroglial cells: physiological properties and a potassium mediated effect of neuronal activity on the glial membrane potential.Proc. Roy. Soc. B 1681–21.

    Google Scholar 

  • Kuffler, S. W., Nicholls, J. G., and Orkand, R. K. (1966). Physiological properties of glial cells in the central nervous system of amphibia.J. Neurophysiol. 29768–787.

    Google Scholar 

  • Kukes, G., Elul, R., and de Vellis, J. (1976). The ionic basis of the membrane potential in a rat glial cell line.Brain Res. 10471–92.

    Google Scholar 

  • Landis, D. M. D., and Reese, T. S. (1981). Membrane structure in mammalian astrocytes: A review of freeze-fracture studies on adult, developing, reactive and cultured astrocytes.J. Exp. Biol. 9535–48.

    Google Scholar 

  • Levitt, P., and Rakic, P. (1980). Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain.J. Comp. Neurol. 193815–840.

    Google Scholar 

  • Lim, R., Mitsunobu, K., and Li, W. K. P. (1973). Maturation-stimulating effect of brain extract and dibutyryl cyclic AMP on dissociated embryonic brain cells in culture.Exp. Cell Res. 79243–246.

    Google Scholar 

  • Lim, R., Troy, S. S., and Turriff, D. E. (1977). Fine structure of cultured glioblasts before and after stimulation by a glia maturation factor.Exp. Cell Res. 106357–372.

    Google Scholar 

  • Lindsay, R. M., Barber, P. C., Sherwood, M. R. C., Zimmer, J., and Raisman, G. (1982). Astrocyte cultures from adult rat brain. Derivation, characterization and neurotropic properties of pure astroglial cells from corpus callosum.Brain Res. 243329–343.

    Google Scholar 

  • Manthorpe, M., Adler, R., and Varon, S. (1979). Development, reactivity and GFA immunofluorescence of astrologia-containing monolayer cultures from rat cerebrum.J. Neurocytol. 8605–621.

    Google Scholar 

  • McCarthy, K. D., and de Vellis, J. (1978). Alpha-adrenergic receptor modulation of beta-adrenergic, adenosine and prostaglandin E1 increased adenosine 3′:5′-cyclic monophosphate levels in primary cultures of glia.J. Cyclic Nucleotide Res. 415–26.

    Google Scholar 

  • Moonen, G., Heinen, E., and Goessens, G. (1976). Comparative ultrastructural study of the effects of serum-free medium and dibutyryl cyclic AMP on newborn rat astroblasts.Cell Tissue Res. 167221–227.

    Google Scholar 

  • Moonen, G., Franck, G., and Schoffeniels, E. (1980). Glial control of neuronal excitability in mammals. I. Electrophysiological and isotopic evidence in culture.Neurochem. Intl. 2299–310.

    Google Scholar 

  • Morrison, R. S., and de Vellis J. (1981). Growth of purified astrocytes in a chemically defined medium.Proc. Natl. Acad. Sci. USA 787205–7209.

    Google Scholar 

  • Narumi, S., Kimelberg, H. K., and Bourke, R. S. (1978). Effects of norepinephrine on the morphology and some enzyme activities of primary monolayer cultures from rat brain.J. Neurochem. 311479–1490.

    Google Scholar 

  • Nicholls, J. G., and Kuffler, S. W. (1964). Extracellular space as a pathway for exchange between blood and neurons in the central nervous system of the leech: Ionic composition of glial cells and neurons.J. Neurophysiol. 27645–671.

    Google Scholar 

  • Noske, W., Lentzen, H., and Herken, H. (1982). Phagocytosis and morphological development of rat astrocytes in primary cultures.Cell Mol. Biol. 28235–244.

    Google Scholar 

  • Orkand, R. K. (1977). Glial cells. InHandbook of Physiology—The Nervous System.Vol. I (Kandel, E. R., Ed.), American Physiological Society, Bethesda, Md., pp. 855–875.

    Google Scholar 

  • Pelton, E. W., Kimelberg, H. K., Shipherd, S. V., and Bourke, R. S. (1981). Dopamine and norepinephrine uptake and metabolism by astroglial cells in culture.Life Sci. 281655–1663.

    Google Scholar 

  • Peters, A., Palay, S. L., and Webster, H. de F. (1976).The Fine Structure of the Nervous System: The Neurons and Supporting Cells, W. B. Saunders, Philadelphia, London, Toronto, pp. 231–263.

    Google Scholar 

  • Picker, S., Pieper, C. F., and Goldring, S. (1981). Glial membrane potentials and their relationship to [K+]o in man and guinea pig.J. Neurosurg. 55347–363.

    Google Scholar 

  • Pope, A. (1978) Neuroglia: Quantitative aspects. InDynamic Properties of Glia Cells (Schoffeniels, E., Franck, G., Hertz, L., and Tower, D. B., Eds.), Pergamon Press, Oxford, New York, pp. 13–20.

    Google Scholar 

  • Raju, T., Bignami, A., and Dahl, D. (1981). In vivo and in vitro differentiation of neurons and astrocytes in the rat embryo.Dev. Biol. 85344–357.

    Google Scholar 

  • Ransom, B. R., Neale, E., Henkart, M., Bullock, P. N., and Nelson, P. G. (1977). Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.J. Neurophysiol. 401132–1150.

    Google Scholar 

  • Reiser, G., Löffler, F., and Hamprecht B. (1983). Tetrodotosun-sensitive ion channels characterized in glial and neuronal cells from rat brain.Brain Res. 261335–340.

    Google Scholar 

  • Sensenbrenner, M. (1977). Dissociated brain cells in primary cultures. InCell, Tissue and Organ Cultures in Neurobiology (Federoff, S., and Hertz, L., Eds.), Academic Press, New York, pp. 191–213.

    Google Scholar 

  • Shapiro, D. L. (1973). Morphological and biochemical alterations in foetal rat brain cells cultured in the presence of monobutyryl cyclic AMP.Nature 241203–204.

    Google Scholar 

  • Shein, H. M. (1965). Propagation of human fetal spongioblasts and astrocytes in dispersed cell cultures.Exp. Cell Res. 40554–569.

    Google Scholar 

  • Somjen, G. G. (1975). Electrophysiology of neuroglia.Annu. Rev. Physiol. 37163–190.

    Google Scholar 

  • Somjen, G. G. (1981). Physiology of glial cells. InAdvances in Physiological Science 3, Physiology of Non-excitable Cells (Salanki, J., Ed.), Pergamon Press, Oxford, New York, pp. 23–43.

    Google Scholar 

  • Stieg, P. E., Kimelberg, H. K., Mazurkiewicz, J. E., and Banker, G. A. (1980). Distribution of glial fibrillary acidic protein and fibronectin in primary astroglial cultures from rat brain.Brain Res. 199493–500.

    Google Scholar 

  • Suddith, R. L., Hutchison, H. T., and Haber, B. (1978). Uptake of biogenic amines by glial cells in culture. I. A neuronal-like transport system for serotonin.Life Sci. 222179–2188.

    Google Scholar 

  • Tardy, M., Costa, M. F. D., Fages, C., Bardakdjian, J., and Gonnard, P. (1982). Uptake and binding of serotonin by primary cultures of mouse astrocytes.Dev. Neurosci. 519–26.

    Google Scholar 

  • Terasaki, W. L., Brooker, G., de Vellis, J., Inglish, D., Hsu, C-H, and Moylan, R. D. (1978). Involvement of cyclic AMP and protein synthesis in catecholamine refractoriness.Adv. Cyclic Nucleotide Res. 933–52.

    Google Scholar 

  • Trachtenberg, M. C., and Pollen, D. A. (1970). Neuroglia: Biophysical properties and physiologic function.Science 1671248–1251.

    Google Scholar 

  • Trimmer, P. A., Reier, P. J., Oh, T. H., and Eng, L. F. (1982). An ultrastructural and immunocytochemical study of astrocytic differentiationin vitro.J. Neuroimmunol. 2235–260.

    Google Scholar 

  • Van Calker, D., and Hamprecht, B. (1980). Effects of neurohormones on glial cells. InAdvances in Cellular Neurobiology, Vol. 1 (Federoff, S., and Hertz, L., Eds.), Academic Press, New York, pp. 31–67.

    Google Scholar 

  • Van Calker, D., Muller, M., and Hamprecht, B. (1978). Adrenergicα- andβ-receptors expressed by the same cell type in primary culture of perinatal mouse brain.J. Neurochem. 30713–718.

    Google Scholar 

  • Varon, S. (1975). Neurons and glia in neural cultures.Exp. Neurol. 4893–134.

    Google Scholar 

  • Varon, S., and Somjen, G. G. (1979). Neuron-glia interactions.Neurosci. Res. Prog. Bull. 171–239.

    Google Scholar 

  • Walz, W., and Hertz, L. (1982). Ouabain-sensitive and ouabain-resistant net uptake of potassium into astrocytes and neurons in primary cultures.J. Neurochem. 3970–77.

    Google Scholar 

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Kimelberg, H.K. Primary astrocyte cultures—a key to astrocyte function. Cell Mol Neurobiol 3, 1–16 (1983). https://doi.org/10.1007/BF00734994

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