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  • Research reportCNTF induces GFAP in a S-100α brain cell population: the pattern of CNTF-αR suggests an indirect mode of action
  • Add time:08/21/2019         Source:sciencedirect.com

    In a recent report, we demonstrated that intracerebral injections of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), into developing postnatal rats evoked a severe inflammatory response as determined by the appearance of reactive astrocytes and activated microglia. Considering the likely involvement of CNTF in the injury response, we felt it was important to further understand the role of CNTF in the developing rat CNS. In this study, we examined the responsiveness of other cell populations to intracerebral injections of CNTF. We report that CNTF increases glial fibrillary acidic protein (GFAP), while having no appreciable effect on the levels of other intermediate filaments including vimentin and neurofilament. Moreover, CNTF did not affect the expression of the mature oligodendrocyte gene, myelin basic protein. These results suggest that CNTF is highly specific in its regulation of GFAP. In our previous study, we showed CNTF to increase GFAP in a cell population that already exists in the CNS parenchyma. To determine the origin of the CNTF-induced reactive astrocytes, therefore, we have utilized a technique of combined in situ hybridization and immunocytochemistry. To examine the possibility that CNTF acts on oligodendrocyte precursors to give rise to reactive astrocytes, the platelet-derived growth factor alpha receptor (PDGF-αR) was utilized as a riboprobe in conjunction with an antibody to GFAP. Examination of CNTF-induced GFAP + astrocytes revealed no colocalization with PDGF-αR mRNA. In contrast, when we utilized an S100α antibody recognizing a calcium binding protein in immature astrocytes, we found colocalization of S100α and GFAP mRNA. These data suggest that CNTF induces an upregulation of GFAP in immature S100α + astrocytes. Examination of the CNTF-α receptor mRNA revealed no change in expression following CNTF treatment. Unexpectedly, however, the CNTF-induced astrogliotic response appears to be indirect since the CNTF-α receptor was solely expressed by neurons in the cytokine-treated animals.

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