Abstract
Glial fibrillary acidic protein (GFAP), the major component of the intermediate filament in differentiated astrocytes (Eng et al., 1971; Eng, 1985), is extensively synthesized within and adjacent to the site of injury (Eng, 1988a; Condorelli et al., 1990; Hozumi et al., 1990; Vijayan et al., 1990). Other than GFAP accumulation, astrogliosis is also characterized by astrocyte proliferation (hyperplasia) and extensive hypertrophy of the cell body, nucleus as well as cytoplasmic processes (Eng, 1988a). Astrogliosis may participate in the healing phase following CNS injury by actively monitoring and controlling the molecular and ionic contents of the extracellular space of the CNS. They can wall off areas of the CNS that are exposed to non-CNS tissue environments following trauma. On the other hand, such responses may interfere with the function of residual neuronal circuits, by preventing remyelination, or by inhibiting axonal regeneration (Eng et al., 1987; Stensaas et al., 1987; Reier and Houle, 1988). Although astrogliosis has received considerable attention in term of its proposed inhibitory effect on CNS repair, there is still very little specific information available concerning the properties of reactive astrocytes, what triggers glial reactivity, and many of the cellular dynamics associated with scar formation. Control of astrocyte proliferation, differentiation, and astrogliosis may be linked to GFAP synthesis. Our aim was to transfect astrocytes with exogenous synthetic oligo- or polynucleotides, which would allow the manipulation of a transient suppression of GFAP synthesis which might delay the gliotic reaction and the scar formation, thus allowing neurons and oligodendrocytes to re-establish a functional environment.
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References
Barrett, J.C., Miller, P.S., and Ts’o, P.O.P., 1974, Inhibitory effect of complex formation with oligodeoxyribonucleotide ethyl phosphotriesters on transfer ribonucleic acid amino-acylation, Biochemistry 13: 4897.
Calabretta, B., Sims, R.B., Valtieri, M., Caracciolo, D., Szczylik, C., Venturelli, D., Ratalczak, M., Beran, M., and Gewirtz, A.M., 1991, Normal and leukemic hematopoietic cells manifest differential sensitivity to inhibitory effects of c-myb antisense oligodeoxynucleotides: An in vitro study relevant to bone marrow purging, Proc. Natl. Acad. Sci. USA 88: 2351.
Chiang, M-Y., Chan, H., Zounes, M.A., Freier, S.M., Lima, W.F., and Bennett, C.F., 1991, Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms, J. Biol. Chem. 266: 18162.
Chiu, F.C., and Goldman, L.E., 1985, Regulation of glial fibrillary acidic protein ( GFAP) expres- sion in CNS development and in pathological states, J. Neuroimmunol. 8: 283.
Chrisey, L.A., 1990, Antisense, in: “Synthecell Synthesis,” Vol. 2, Synthecell Corp, MD, USA. Cohen, J.S., 1989, “Oligodeoxynucleotides. Antisense Inhibitors of Gene Expression. Topics in Molecular and Structural Biology,” CRC Press, Boca Raton, Florida.
Condorelli, D.F., Dell’Albani, P., Kaczmarek, L., Messina, L., Spampinato, G., Avola, R., Messina, A., and Giuffrida Stella, A.M., 1990, Glial fibrillary acidic protein messenger RNA and glutamine synthetase activity after nervous system injury, J. Neurosci. Res. 26: 251.
Day, A.G., Bejarano, E.R., Buck, K.W., Burrell, M., and Lichtenstein, C.P., 1991, Expression of an antisense viral gene in transgenic tobacco confers resistance to the DNA virus tomato golden mosaic virus, Proc. Natl. Acad. Sci. USA 88: 6721.
DeArmond, S.J., Lee, Y-L., Kretzschmar, H.A., and Eng, L.F., 1986, Turnover of glial filaments in mouse spinal cord, J. Neurochem. 47: 1749.
Eng, L.F., 1985, Glial fibrillary acid protein (GFAP): The major protein of glial intermediate filaments in differentiated astrocytes, J. Neuroimmunol. 8: 203.
Eng, L.F., 1988a, Astrocytic response to injury, in: “Current Issues in Neural Regeneration Research,” P. Reier, R. Bunge, and R. Seil, ed., Alan R. Liss, New York.
Eng, L.F., 1988b, Regulation of glial intermediate filaments in astrogliosis, in: “The Biochemical Pathology of Astrocytes,” M.D. Norenberg, L. Hertz, and A. Schousboe, ed., Alan R. Liss, New York.
Eng, L.F., 1992, Current antisense nucleic acid strategies for manipulating neuronal and glial cells, in: “Molecular and Cellular Approaches to the Treatment of Brain Diseases,” S. G. Waxman, ed., Raven Press, New York.
Eng, L.F., Reier, P.J., and Houle, J.D., 1987, Astrocyte activation and fibrous gliosis: Glial fibrillary acidic protein immunostaining of astrocytes following intraspinal cord grafting of fetal CNS tissue, Prog. Brain Res. 71: 439.
Eng, L.F., Stticklin, E., Lee, Y-L., Shiurbo, R.A., Coria, F., Halks-Miller, M., Mozsgau, C., Fukayama, G., and Gibbs, M., 1986, Astrocyte culture on nitrocellulose membranes and plas- tic: Detection of cytoskeletal proteins and mRNA by immunocytochemistry and in situ hybridization, J. Neurosci. Res. 16: 239.
Eng, L.F., Vanderhaeghen, J.J., Bignami, A., and Gerstl, B., 1971, An acidic protein isolated from fibrous astrocytes, Brain Res. 28: 351.
Feigner, P.L., and Holm, M., 1989, Cationic liposome-mediated transfection, Focus 11: 21.
Feigner, P.L., and Ringold, G.M., 1989, Cationic liposome-mediated transfection, Nature 337: 387.
Gagnor, C., Rayner, B., Leonetti, J-P., Imbach, J-L., and Lebleu, B., 1989, a-DNA IX. Parallel annealing of a-anomeric oligodeoxyribonucleotides to natural mRNA is required for interference in RNase H mediated hydrolysis and reverse transcription, Nucl. Acids Res. 17: 5107.
Goldman, J.E., and Chiu, F-C., 1984, Dibutyryl cyclic AMP causes intermediate filament ac- cumulation and actin reorganization in primary astrocytes, Brain Res. 306: 85.
Goodchild, J., 1990, Conjugates of oligonucleotides and modified oligonucleotides: A review of their synthesis and properties, Bioconjugate Chemistry 1: 165.
Han, L., Yun, J.S., and Wagner, T.E., 1991, Inhibition of Moloney murine leukemia virus-induced leukemia in transgenic mice expressing antisense RNA complementary to the retroviral packaging sequences, Proc. Natl. Acad. Sci. USA 88: 4313.
Helene, C., and Toulme, J-J., 1990, Specific regulation of gene expression by antisense, sense, and antigen nucleic acids, Biochim. Biophys. Acta 1049: 99.
Hertz, L., Bock, E., and Schousboe, A., 1978, GFA content, glutamate uptake and activity of glutamate metabolizing enzymes in differentiating mouse astrocytes in primary cultures, Dev. Neurosci. 1: 226.
Hozumi, I., Chiu, F-C., and Norton, W.T., 1990, Biochemical and immunocytochemical changes in glial fibrillary acidic protein after stab wounds, Brain Res. 524: 64.
Lavignon, M., Bertrand, J-R., Rayner, B., Imbach, J-L., Malvy, C., and Paoletti, C., 1989, Inhibition of Moloney murine leukemia virus reverse transcriptase by a-anomeric oligonucleotides, Biochem. Biophys. Res. Comm. 161: 1184.
Le Doan, T., Chavany, C., and Helene, C., 1989, Antisense oligonucleotides as potential antiviral and anticancer agents, Bull. Cancer 76: 849.
Le Prince, G., Fages, C., Rolland, B., Nunez, J., and Tardy, M., 1991, DBcAMP effect on the expression of GFAP and of its encoding mRNA in astroglial primary cultures, Glia 4: 322.
Lewis, S.A., Balcarek, J.M., Krek, V., Shelanski, M., and Cowan, N.J., 1984, Sequence of a cDNA clone encoding mouse glial fibrillary acidic protein: structural conservation of intermediate filaments, Proc. Natl. Acad. Sci. USA 81: 2743.
Mannino, R J, and Gould-Fogente, S., 1988, Liposome mediated gene transfer, BioTechniques 6: 628.
Manson, J., Brown, T., and Duff, G., 1990, Modulation of interleukin 1 beta gene expression using antisense phosphorothioate oligonucleotides, Lymphokine Res. 9: 35.
Maurer, R.A., 1989, Cationic liposome-mediated transfection of primary cultures of rat pituitary cells, Focus 11: 2527.
Miller, P.S., Barrett, J.C., and Ts’o, P.O.P., 1974, Synthesis of oligodeoxyribonucleotide ethyl phosphotriesters and their specific complex formation with transfer ribonucleic acid, Biochemistry 13: 4887.
Mol, J.N.M., and van der Krol, A., 1991, “Antisense Nucleic Acids and Proteins. Fundamentals and Applications,” Marcel Dekker, New York.
Morrison, R.S., de Vellis, J., Lee, Y.L., Bradshaw, R.A., and Eng, L.F., 1985, Hormones and growth factors induce the synthesis of glial fibrillary acidic protein in rat brain astrocytes, J. Neurosci. Res. 14: 167.
Nicolau, C., and Cudd, A., 1989, Liposomes as carriers of DNA, Crit. Rev. Ther. Drug Carrier Syst. USA 6: 239.
Owens, G.C., and Boyd, C.J., 1991, Expressing antisense Po RNA in Schwann cells perturbs myelination, Development 112: 639.
Owens, G.C., and Bunge, R.P., 1991, Schwann cells infected with a recombinant retrovirus expressing myelin-associated glycoprotein antisense RNA do not form myelin, Neuron 7: 565.
Papahadjopoulos, D., 1988, Liposome formation and properties: an evolutionary profile, Biochem. Soc. Trans. England 16: 910.
Paterson, B.M., Roberts, B.E., and Kuff, E.L., 1977, Structural gene identification and mapping by DNA mRNA hybrid-arrested cell-free translation, Proc. Natl. Acad. Sci. USA 74: 4370.
Potter, H., Weir, L., and Leder, P., 1984, Enhancer dependent expression of human k im- munoglobulin genes introduced into mouse pre-B lymphocytes by electroporation, Proc. Natl. Acad. Sci. USA 81: 7161.
Price, J., and Thurlow, L., 1988, Cell lineage in rat cerebral cortex: a study using retroviralmediated gene transfer, Development 104: 473.
Reier, P.J., and Houle, J.D., 1988, The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair, in: “Physiological Basis for Functional Recovery in Neurological Disease,” S.G. Waxman, ed., Raven Press, New York.
Selden, R.F., Burko-Howie, K., Rowe, M.E., Goodman, H.M., and Moore, D.D., 1986, Human growth hormone as a receptor gene in regulation studies employing transient gene expression, Mol. Cell Biol. 6: 3173.
Shafit-Zagardo, B., Kume-Iwaki, A., and Goldman, J.E., 1988, Astrocytes regulate GFAP Mrna levels by cyclic AMP and protein kinase C-dependent mechanisms, Glia 1: 346.
Smith, M.E., Perret, V., and Eng, L.F., 1984, Metabolic studies in vitro of the CNS cytoskeletal proteins: Synthesis and degradation, Neurochem. Res. 9: 1493.
Stensaas, L.J., Partlow, L.M., Burgess, P.R., and Horch, K.W., 1987, Inhibition of regeneration: The ultrastructure of reactive astrocytes and abortive axon terminals in the transition zone of the dorsal root, Prog. Brain Res. 71: 457.
Krol, A.R., Mol, J.N.M., and Stuitje, A.R., 1988, Modulation of eukaryotic gene expression by complementary RNA or DNA sequences, BioTechniques 6: 958.
Vijayan, V.K., Lee, Y.L., and Eng, L.F., 1990, Increase in glial fibrillary acidic protein following neural trauma, Mol. Chem. Neuropath. 13: 111.
Weinstein, D.E., Shelanski, M.L., and Liem, R.K.H., 1991, Suppression by antisense mRNA demonstrates a requirement for the glial fibrillary acidic protein in the formation of stable astrocytic processes in response to neurons, J. Cell Biol. 112: 1205.
Wigler, M., Pellicer, A., Silverstein, S., and Axel, R., 1978, Biochemical transfer of single-copy eukaryotic genes using total cellular DNA as donor, Cell 14: 725.
Yu, A.C.H., Gregory, G.A., and Chan, P.K., 1989, Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures, J. Cereb. Blood Flow Metab. 9: 20.
Yu, A.C.H., Lee, Y.L., and Eng, L.F., 1991, Inhibition of GFAP synthesis by antisense mRNA in astrocytes, J. Neurosci. Res. 30: 72.
Yu, A.C.H., Lee, Y.L., and Eng, L.F., 1993, Astrogliosis in culture: I. The model and the effect of antisense oligonucleotide on glial fibrillary acidic protein synthesis. J. Neurosci. Res. ( In press )
Zamecnik, P.C., and Stephenson, M.L., 1978, Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide, Proc. Natl. Acad. Sci. USA 75: 280.
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Yu, A.C.H., Lee, Y.L., Eng, L.F. (1993). Inhibition of GFAP Synthesis with Antisense Nucleic Acid Constructs. In: Fedoroff, S., Juurlink, B.H.J., Doucette, R. (eds) Biology and Pathology of Astrocyte-Neuron Interactions. Altschul Symposia Series, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9486-1_28
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