Astrogliosis in culture: I. The model and the effect of antisense oligonucleotides on glial fibrillary acidic protein synthesis
- 15 February 1993
- journal article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 34 (3), 295-303
- https://doi.org/10.1002/jnr.490340306
Abstract
Astrogliosis is a predictable response of astrocytes to various types of injury caused by physical, chemical, and pathological trauma. It is characterized by hyperplasia, hypertrophy, and an increase in immunodetectable glial fibrillary acidic protein (GFAP). As GFAP accumulation is one of the prominent features of astrogliosis, inhibition or delay in GFAP synthesis in damaged and reactive astrocytes might affect astrogliosis and delay scar formation. The aim of this study is to investigate the possibility of utilizing antisense oligonucleotides in controlling the response of astrocytes after mechanically induced injury. We scratched primary astrocyte cultures prepared from newborn rat cerebral cortex with a plastic pipette tip as an injury model and studied the astrogliotic responses in culture. Injured astrocytes became hyperplastic, hypertrophic, and had an increased GFAP content. These observations demonstrate that injured astrocytes in culture are capable of becoming reactive and exhibit gliotic behaviors in culture without neurons. The increase in GFAP content in injured astrocytes could be inhibited by incubating the scratched culture with commerically available liposome complexed with 3′ or 5′ antisense oligonucleotides (20 nt) in the coding region of mouse GFAP. The scratch model provides a simple system to examine in more detail the mechanisms involved in triggering glial reactivity and many of the cellular dynamics associated with scar formation. Antisense oligonucleotide treatment could inhibit the GFAP synthesis in injured astrocytes, hence it may be applicable in modifying scar formation in CNS injury in vivo.Keywords
This publication has 29 references indexed in Scilit:
- Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetiiCellular Microbiology, 2007
- Inhibition of GFAP synthesis by antisense RNA in astrocytesJournal of Neuroscience Research, 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.The Journal of cell biology, 1991
- Glial fibrillary acidic protein messenger RNA and glutamine synthetase activity after nervous system injuryJournal of Neuroscience Research, 1990
- Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in ratsDevelopmental Brain Research, 1988
- Turnover of Glial Filaments in Mouse Spinal CordJournal of Neurochemistry, 1986
- Astrocyte culture on nitrocellulose membranes and plastic: Detection of cytoskeletal proteins and mRNAs by immunocytochemistry and in situ hybridizationJournal of Neuroscience Research, 1986
- Hormones and growth factors induce the synthesis of glial fibrillary acidic protein in rat brain astrocytesJournal of Neuroscience Research, 1985
- Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.Proceedings of the National Academy of Sciences, 1979
- ASTROCYTE MITOSES AND ALZHEIMER TYPE I AND II ASTROCYTES IN ANOXIC ENCEPHALOPATHYNeuropathology and Applied Neurobiology, 1976