Regulation of Gene Expression in Astrocytes

  • Jean de Vellis
Part of the Altschul Symposia Series book series (ALSS, volume 2)


The astrocytes are the most functionally diversified and phenotypically plastic cells in the central nervous system (CNS). Unlike neurons they are not terminally differentiated nor are they as functionally specialized as the oligodendrocytes. Astrocytes ensheathe neuronal dendrites, somas and synaptic surfaces. They also extend processes to the nodes of Ranvier, the pia mater forming the glial limitans, and to all brain capillaries. Thus the astrocytes “fence in” the brain parenchyma. These extensive and close anatomic associations of astrocytes with neurons and capillaries position these cells as the gate keepers to the brain parenchyma, suggesting that they are target cells for stimuli from peripheral as well as central origin. During the last 15 years, cultured astrocyte preparations have provided an excellent system to study responses to a large number of mitogenic and differentiation signals. These studies have begun to reveal the nature of neuron-astrocyte and astrocyte-endothelial cells/periphery coupling. For instance, radioligand receptor studies and electrophysiological investigations of receptor and ion channels have revealed the existence of receptors on astrocytes for nearly all the types of neurotransmitters and neuromodulators involved in neuronal communication (Kimelberg and Norenberg, 1988; Kimelberg, 1988). A wide range of mitogenic factors have been shown to cause proliferation of cultured astrocytes (for review see Arenander and de Vellis, 1989; Arenander et al. 1989b). Agents that increase intracellular cyclic AMP or stimulate protein kinase C activity induce stellation of astrocytes in culture. Their morphological and biochemical phenotype is also regulated by classical hormones (for review, de Vellis et al., 1986), growth factors (Morrison et al., 1985), neurotransmitters (McCarthy et al., 1988b) and retinoic acid (Wuarin et al, 1990). The most widely studied gene regulation in astrocytes is the hydrocortisone induction of glutamine synthetase. Its expression is also regulated in a complex way by many agents, including neuronal surface antigens (Wu et al., 1985; for review see Kumar and de Vellis, 1987; de Vellis et al. 1986). Surprisingly, neurotrophins, such as nerve growth factor (NGF), which were thought to act only on certain types of neurons, have recently been reported to affect astrocyte physiology and upregulate the expression oflow and high affinity NGF receptors (Kumar et al. 1990; 1992).


Nerve Growth Factor Fibroblast Growth Factor Glutamine Synthetase Neurotrophin Receptor Early Response Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamo, M., Raizada, M.K. and LeRoith, D., 1989. Insulin and insulin-like growth factor receptors in the nervous system. Mol. Neurobiol. 3: 71–95.PubMedCrossRefGoogle Scholar
  2. Aizenman, Y. and de Vellis, J., 1987. Synergistic action of thyroid hormone, insulin and hydrocortisone on astrocyte differentiation. Brain Res. 414: 301–308.PubMedCrossRefGoogle Scholar
  3. Arenander, A., R. Lim, B. Vamum, R. Cole, H. R. Herschman and J. de Vellis. (1988). Astrocyte response to growth factors and hormones: Early molecular events, in: “Current Issues in Neural Regeneration Research”, P. J. Reier, R. P. Bunge and F. J. Seil, eds., Alan R. Liss, Inc., N.Y., pp. 257–269.Google Scholar
  4. Arenander, A. and de Vellis, J. (1989). Development of the nervous system, in: “Basic Neurochemistry: Molecular, Cellular and Medical Aspects”, 4th ed., G. J. Siegel et al., eds., Raven Press, Ltd., N.Y. pp. 479–506.Google Scholar
  5. Arenander, A. T., de Vellis, J. and Herschman, H.R. 1989a. Induction of c-fos and TIS genes in cultured rat astrocytes by neurotransmitters. J. Neurosci. Res. 24: 107–114.PubMedCrossRefGoogle Scholar
  6. Arenander, A. T., Lin, R.W., Vamum, B.C., Cole, R., de Vellis, J. and Herschman, H.R., 1989b. T1S gene expression in cultured rat astrocytes: Induction by mitogens and stellation agents. J. Neurosci. Res. 23: 247–256.PubMedCrossRefGoogle Scholar
  7. Arenander, A. T., Lim, R.W., Vamum, B.C., Cole, R., de Vellis, J. and Herschman, H.R., 1989e. TIS gene expression in cultured rat astrocytes: Multiple pathways of induction by mitogens. J. Neurosci. Res. 23: 257–265.PubMedCrossRefGoogle Scholar
  8. Arenander, A., Cheng, J. and de Vellis, J., 1991. Early events in the hormonal regulation of glial gene expression: Early response genes, in: “Insulin, IGFs and their Receptors”, M. Raizada and D. LeRoith, eds., Plenem Press, New York. pp. 335–350.Google Scholar
  9. Arenander, A.T. and Herschman, H.R. (1991). Primary response gene expression in the nervous system, in:“Neurotrophic Factors”, J.H. Fallon and S.E. Loughlin, eds., Academic Press, New York, in press.Google Scholar
  10. Arenander, A. and de Vellis, J., 1992a. Early response gene induction in astrocytes as a mechanism for encoding and integrating neuronal signals, in:“Neuronal-Astrocytic Interactions: Pathological Implications”, A. Yu, L. Hertz, M. Norenberg, E. Sykova and S. Waxman, eds., Progress in Brain Research. (in press).Google Scholar
  11. Arenander, A. and de Vellis, J., 1992b. Early Response Gene Expression Signifying Functional Coupling of Neuroligand Receptor Systems in Astrocytes, in:“Astrocytes:Phannacology and Function”, S. Murphy, ed., Academic Press, New York. (in press).Google Scholar
  12. Arenander, A.T. and Herschman, H.R., 1993. Primary Response Gene Expression in the Nervous System, in: “Neurotrophic Factors”, S.E. Loughlin and J.H. Fallon, eds., Academic Press, New York, pp. 89–128.Google Scholar
  13. Blackshear, P.J., Stumpo, D.J., Huang, J-K., Nemenoff, R.A. and Spach, D.H. (1987) Protein kinase C-dependent and -independent pathways of proto-oncogene induction in human astrocytoma cells. J. Biol. Chem., 262: 7774–7781.PubMedGoogle Scholar
  14. Cancilla, P.A., Bready, J., Berliner, J., Sharifi-Nia, H. Toga, A.W., Santon, E.M., Scully, S. and de Vellis, J. 1992. Expression of mRNA for glial fibrillary acidic protein after experimental cerebral injury. J Neuropathology Experimental Neurology 51: 560–565.CrossRefGoogle Scholar
  15. Condorelli, D., Kaczmarek, L., Nicoletti, F., Arcidiacono, P., Dell’Albani, P., lngrao, F.,Magri, G. Malaguameara, L., Avola, R., Messina, A., and Giuffrida-Stella, A.M., 1989. Induction of proto-oncogene fos by extracellular signals in primary glial cellcultures. J. Neurosci. Res. 23: 234–239.Google Scholar
  16. de Vellis, J. and Brooker, G., 1974. Reversal of catecholamúie refractoriness by inhibitors of RNA and protein synthesis. Science 186: 1221–1223.CrossRefGoogle Scholar
  17. de Vellis, J., Wu, D.K. and S. Kumar. (1986). Enzyme induction and regulation of protein synthesis, in: “Astrocytes”, Vol. 2. S. Fedoroff and A. Vernadakis, eds., Academic Press, pp. 209–237.Google Scholar
  18. Dwyer, B.E., Nishimura, R.N., de Vellis, J., and Yoshida, T. (1992) Heine Oxygenase is a heat shock protein and PEST protein in rat astroglial cells. Glia 5: 300–305.PubMedCrossRefGoogle Scholar
  19. Hamprecht, B., 1986. Astroglial cells in culture: Receptors and cyclic nucleotides in astrocytes, in: “Astrocytes”, S. Federoff and A. Vernadakis, eds. Academic Press, New York, pp. 77–106.Google Scholar
  20. Herschman, H.R., 1991. Primary response genes induced by growth factors and tumor promoters, in: “Annual Reviews of Biochemistry”, C. Richardson, ed., Vol. 60, pp. 281–319. Annual Reviews, Palo Alto, California.Google Scholar
  21. Kimelberg, H. and Norenberg, M., 1989. Astrocytes. Sci. Amer. 260: 66–72.PubMedCrossRefGoogle Scholar
  22. Kimelberg, H., 1988. Glial Cell Receptors. H. Kimelberg, ed., Raven Press, New York, p. 275. Kumar, S. and J. de Vellis. (1987). Glucocorticoid mediated functions in glial cells, in: “Glial Cell Receptors”, H. K. Kimelberg, ed., Raven Press, New York, pp. 243–263.Google Scholar
  23. Kumar, S., J. Huber, L. A. Pena, J. de Vellis. 1990. Characterization of Functional Nerve Growth Factor-Receptors in a CNS Glial Cell Line: Monoclonal Antibody 217e Recognizes the Nerve Growth Factor-Receptor on C6 Glioma Cells..L Neurosci.Res. 27: 408–417.CrossRefGoogle Scholar
  24. Kumar, S., Pena., L.A., and de Vellis, J. 1993. CNS glial cells express neurotrophin receptors whose levels are regulated by NGF. Molecular Brain Res. (in press).Google Scholar
  25. 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. 4: 15–26.PubMedGoogle Scholar
  26. McCarthy, K. D. and de Vellis, J., 1979. The regulation of adenosine 3’:5’- cyclic monophosphate accumulation in glia by alpha-adrenergic agonists. Life Sci. 24: 639–650.PubMedCrossRefGoogle Scholar
  27. McCarthy, K. D. and de Vellis, J., 1980. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 85: 8790–902.CrossRefGoogle Scholar
  28. McCarthy, K.D., Lerea, L.S. and Salm, A.K., 1988a. Pharmacology of Astroglia, in: “The Biochemical Pathology of Astrocytes”, Alan Liss, New York, pp. 543–555.Google Scholar
  29. McCarthy, K.D., Salm, A.K. and Lerea. L.S., 1988b. Astroglial receptors and their regulation of intermediate filament protein phosphorylation, in: “Glial Cell Receptors”, H.K. Kimelberg, ed., Raven Press, New York, pp. 243–263.Google Scholar
  30. Morrison, R. S. and de Vellis,J., 1981. Growth of purified astrocytes in a chemically defined medium. Proc. Nail. Acad Sci., USA 78: 7205–7209.CrossRefGoogle Scholar
  31. Morrison, R. S., de Vellis, J., Lee, Y.L., Bradshaw, R.A. and Eng. L.A., 1985. Hormones and growth factors induct the synthesis of glial fibrillary acidic protein ion rat brainastrocytes. I. Neurosci. Res. 143: 167–176.CrossRefGoogle Scholar
  32. Murphy, S. and Pearce, B., 1987. Functional receptors for neurotransmitters on astroglial cells. Neurosci. 22: 381–394.CrossRefGoogle Scholar
  33. Nishimura, R.N., Dwyer, B.E., de Vellis, J. and Clegg, K.B. (1992) Characterization of the major 68 kDa heat shock protein in a rat transformed astroglial cell line. Mol. Brain Res. 12: 203–208.PubMedCrossRefGoogle Scholar
  34. Pearce, B., Cambray-Deakin, M., Morrow, C., Grumble, J. and Murphy, S., 1985. Activation of muscarnnic and of al-adrenergic Receptors on astrocytes results in the accumulation of inositol phosphates. J Neurochem. 45: 1534–1540.PubMedCrossRefGoogle Scholar
  35. Ritchie, T., Cole, R., Kim, R.-S., de Vellis, J. and Noble, E.P.. 1987. Inositol phospholipid hydrolysis in cultured astrocytes and oligodendrocytes. Life Sci. 41: 31–39.PubMedCrossRefGoogle Scholar
  36. Wu, D.K. and de Vellis, J., 1983. Effect of forskolin on primary cultures of astrocytes and oligodendrocytes..1 Cyclic Nucleotide and Protein Phosphorylation Res. (1):59–67.Google Scholar
  37. Wu, D. K., Morrison, R.S. and de Vellis, J., 1985. Modulation of beta-adrenergic response in rat brain astrocytes by serum and hormones. J Cell. Physiol. 122: 73–80.PubMedCrossRefGoogle Scholar
  38. Wu, D., Scully, S. and de Vellis, J., 1988. Induction of glutamine synthetase in rat astrocytes by co-cultivation with embryonic chick neurons. J. Neurochem. 50: 929–935.PubMedCrossRefGoogle Scholar
  39. Wuarin, L., Sidell, N. and de Vellis, J., 1990. Trophic effects of retinoids on spinal cord cells in culture. Intl..1 Devl. Neurosci. 8: 317–326.CrossRefGoogle Scholar
  40. Yamamoto, K. and Alberts, B., 1976. Steroid receptors: Elements for modulation of eukaryotic transcription. Ann. Rev. Biochein. 45: 721–746.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Jean de Vellis
    • 1
  1. 1.Department of Anatomy and Cell Biology Mental Retardation Research CenterUniversity of California Los AngelesUSA

Personalised recommendations