Effect of 6-hydroxydopamine (6-OHDA) on proliferation of glial cells in the rat cortex and striatum: evidence for de-differentiation of resident astrocytes
| Autor: | Daniela Berg, Andreas von Ameln-Mayerhofer, Eva Kueppers, Britta Wachter, Hans-Jochen Wagner, Sonja Schürger, Jens Rolinger |
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| Rok vydání: | 2010 |
| Předmět: |
Doublecortin Protein
Histology Subventricular zone Pathology and Forensic Medicine Rats Sprague-Dawley chemistry.chemical_compound Adrenergic Agents Cell Movement Glial Fibrillary Acidic Protein medicine Animals Progenitor cell Oxidopamine Cell Proliferation Injections Intraventricular Cerebral Cortex Glial fibrillary acidic protein biology Cell Biology Cell Dedifferentiation Nestin medicine.disease Corpus Striatum Rats Astrogliosis Cell biology Doublecortin Ki-67 Antigen medicine.anatomical_structure nervous system chemistry Chondroitin sulfate proteoglycan Astrocytes biology.protein Neuroglia Neuroscience Biomarkers Astrocyte |
| Zdroj: | Cell and Tissue Research. 342:147-160 |
| ISSN: | 1432-0878 0302-766X |
| DOI: | 10.1007/s00441-010-1061-x |
| Popis: | Reactive astrogliosis is the universal response to any brain insult. It is characterized by cellular hypertrophy, up-regulation of the astrocyte marker glial fibrillary acidic protein (GFAP), and proliferation. The source of these proliferating cells is under intense debate. Progenitor cells derived from the subventricular zone (SVZ), cells positive for chondroitin sulfate proteoglycan (NG2(+)), and de-differentiated astrocytes have been proposed as the origin of proliferating cells following injury. We have analyzed the effect of intraventricular-applied 6-hydroxydopamine (6-OHDA) on the proliferation and morphology of astrocytes in rat cortex and striatum by means of immunohistochemistry and confocal laser microscopy. At 4 days post-lesion, GFAP expression increased markedly. A subpopulation of the GFAP(+) cells co-expressed Ki-67, indicating that these cells were proliferating. To investigate whether these cells (1) arose from migrating SVZ progenitor cells, (2) derived from NG2(+) progenitor cells, or (3) de-differentiated from resident astrocytes, we studied the expression of the migration marker doublecortin (Dcx), the oligodendrocyte progenitor marker NG2, and the progenitor markers Nestin and Pax6. The proliferating Ki-67(+) cells co-expressed Nestin and Pax6, whereas no co-expression of Ki-67 with NG2 or the migration marker Dcx was observed. Thus, resident astrocytes de-differentiate, in response to the intraventricular application of 6-OHDA, to a phenotype resembling radial glia cells, which represent transient astrocyte precursors during development. An understanding of the mechanisms of the de-differentiation of mature astrocytes might be useful for designing new approaches to cell therapy in neurodegenerative diseases such as Parkinson's disease. |
| Databáze: | OpenAIRE |
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