Abstract
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Rapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury
Abstract
Neuronal regeneration does generally not occur in the central nervous system (CNS) after injury, which has been attributed to the generation of glial scar tissue. In this report we show that the composition of the glial scar after traumatic CNS injury in rat and mouse is more complex than previously assumed: expression of the intermediate filament nestin is induced in reactive astrocytes. Nestin induction occurs within 48 hours in the spinal cord both at the site of lesion and in degenerating tracts and lasts for at least 13 months. Nestin expression is induced with similar kinetics in the crushed optic nerve. In addition to the expression in reactive astrocytes, we also observed nestin induction within 48 hours after injury in cells close to the central canal in the spinal cord, while nestin expressing cells at later timepoints were found progressively further out from the central canal. This dynamic pattern of nestin induction after injury was mimicked by lacZ expressing cells in nestin promoter/lacZ transgenic mice, suggesting that defined nestin regulatory regions mediate the injury response. We discuss the possibility that the spatiotemporal pattern of nestin expression reflects a population of nestin positive cells, which proliferates and migrates from a region close to the central canal to the site of lesion in response to injury.
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- Aguayo AJ, Rasminsky M, Bray GM, Carbonetto S, McKerracher L, Villegas-Pérez MP, Vidal-Sanz M, Carter DA. Degenerative and regenerative responses of injured neurons in the central nervous system of adult mammals. Philos Trans R Soc Lond B Biol Sci. 1991 Mar 29;331(1261):337–343. [Abstract] [Google Scholar]
- Cattaneo E, McKay R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature. 1990 Oct 25;347(6295):762–765. [Abstract] [Google Scholar]
- Cripe L, Morris E, Fulton AB. Vimentin mRNA location changes during muscle development. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2724–2728. [Europe PMC free article] [Abstract] [Google Scholar]
- Dahlstrand J, Collins VP, Lendahl U. Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res. 1992 Oct 1;52(19):5334–5341. [Abstract] [Google Scholar]
- Dahlstrand J, Zimmerman LB, McKay RD, Lendahl U. Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments. J Cell Sci. 1992 Oct;103(Pt 2):589–597. [Abstract] [Google Scholar]
- Dahlstrand J, Lardelli M, Lendahl U. Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Brain Res Dev Brain Res. 1995 Jan 14;84(1):109–129. [Abstract] [Google Scholar]
- Eddleston M, Mucke L. Molecular profile of reactive astrocytes--implications for their role in neurologic disease. Neuroscience. 1993 May;54(1):15–36. [Europe PMC free article] [Abstract] [Google Scholar]
- Eng LF, Yu AC, Lee YL. Astrocytic response to injury. Prog Brain Res. 1992;94:353–365. [Abstract] [Google Scholar]
- Frautschy SA, Walicke PA, Baird A. Localization of basic fibroblast growth factor and its mRNA after CNS injury. Brain Res. 1991 Jul 12;553(2):291–299. [Europe PMC free article] [Abstract] [Google Scholar]
- Frederiksen K, Jat PS, Valtz N, Levy D, McKay R. Immortalization of precursor cells from the mammalian CNS. Neuron. 1988 Aug;1(6):439–448. [Abstract] [Google Scholar]
- Frederiksen K, McKay RD. Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci. 1988 Apr;8(4):1144–1151. [Europe PMC free article] [Abstract] [Google Scholar]
- Frisén J, Verge VM, Cullheim S, Persson H, Fried K, Middlemas DS, Hunter T, Hökfelt T, Risling M. Increased levels of trkB mRNA and trkB protein-like immunoreactivity in the injured rat and cat spinal cord. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11282–11286. [Europe PMC free article] [Abstract] [Google Scholar]
- Fuchs C, Druger RK, Glasgow E, Schechter N. Differential expression of keratins in goldfish optic nerve during regeneration. J Comp Neurol. 1994 May 8;343(2):332–340. [Abstract] [Google Scholar]
- Giordano S, Glasgow E, Tesser P, Schechter N. A type II keratin is expressed in glial cells of the goldfish visual pathway. Neuron. 1989 May;2(5):1507–1516. [Abstract] [Google Scholar]
- Gomi H, Yokoyama T, Fujimoto K, Ikeda T, Katoh A, Itoh T, Itohara S. Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions. Neuron. 1995 Jan;14(1):29–41. [Abstract] [Google Scholar]
- Hatten ME, Liem RK, Shelanski ML, Mason CA. Astroglia in CNS injury. Glia. 1991;4(2):233–243. [Abstract] [Google Scholar]
- Heins S, Aebi U. Making heads and tails of intermediate filament assembly, dynamics and networks. Curr Opin Cell Biol. 1994 Feb;6(1):25–33. [Abstract] [Google Scholar]
- Hockfield S, McKay RD. Identification of major cell classes in the developing mammalian nervous system. J Neurosci. 1985 Dec;5(12):3310–3328. [Europe PMC free article] [Abstract] [Google Scholar]
- Holder N, Clarke JD, Kamalati T, Lane EB. Heterogeneity in spinal radial glia demonstrated by intermediate filament expression and HRP labelling. J Neurocytol. 1990 Dec;19(6):915–928. [Abstract] [Google Scholar]
- Ip NY, Wiegand SJ, Morse J, Rudge JS. Injury-induced regulation of ciliary neurotrophic factor mRNA in the adult rat brain. Eur J Neurosci. 1993 Jan 1;5(1):25–33. [Abstract] [Google Scholar]
- Ishikawa R, Nishikori K, Furukawa S. Appearance of nerve growth factor and acidic fibroblast growth factor with different time courses in the cavity-lesioned cortex of the rat brain. Neurosci Lett. 1991 Jun 10;127(1):70–72. [Abstract] [Google Scholar]
- Koshinaga M, Sanon HR, Whittemore SR. Altered acidic and basic fibroblast growth factor expression following spinal cord injury. Exp Neurol. 1993 Mar;120(1):32–48. [Abstract] [Google Scholar]
- Landry CF, Ivy GO, Brown IR. Developmental expression of glial fibrillary acidic protein mRNA in the rat brain analyzed by in situ hybridization. J Neurosci Res. 1990 Feb;25(2):194–203. [Abstract] [Google Scholar]
- Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990 Feb 23;60(4):585–595. [Abstract] [Google Scholar]
- Levison SW, Goldman JE. Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron. 1993 Feb;10(2):201–212. [Abstract] [Google Scholar]
- Liem RK. Molecular biology of neuronal intermediate filaments. Curr Opin Cell Biol. 1993 Feb;5(1):12–16. [Abstract] [Google Scholar]
- Lindholm D, Castrén E, Kiefer R, Zafra F, Thoenen H. Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation. J Cell Biol. 1992 Apr;117(2):395–400. [Europe PMC free article] [Abstract] [Google Scholar]
- Logan A, Frautschy SA, Gonzalez AM, Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci. 1992 Oct;12(10):3828–3837. [Europe PMC free article] [Abstract] [Google Scholar]
- Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science. 1994 May 20;264(5162):1145–1148. [Abstract] [Google Scholar]
- McCarthy KD, de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980 Jun;85(3):890–902. [Europe PMC free article] [Abstract] [Google Scholar]
- Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron. 1994 Nov;13(5):1071–1082. [Abstract] [Google Scholar]
- Nilsson E, Lendahl U. Transient expression of a human beta-actin promoter/lacZ gene introduced into mouse embryos correlates with a low degree of methylation. Mol Reprod Dev. 1993 Feb;34(2):149–157. [Abstract] [Google Scholar]
- Pekny M, Levéen P, Pekna M, Eliasson C, Berthold CH, Westermark B, Betsholtz C. Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J. 1995 Apr 18;14(8):1590–1598. [Europe PMC free article] [Abstract] [Google Scholar]
- Redies C, Lendahl U, McKay RD. Differentiation and heterogeneity in T-antigen immortalized precursor cell lines from mouse cerebellum. J Neurosci Res. 1991 Dec;30(4):601–615. [Abstract] [Google Scholar]
- Renfranz PJ, Cunningham MG, McKay RD. Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell. 1991 Aug 23;66(4):713–729. [Abstract] [Google Scholar]
- Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992 Mar 27;255(5052):1707–1710. [Abstract] [Google Scholar]
- Schwab ME, Kapfhammer JP, Bandtlow CE. Inhibitors of neurite growth. Annu Rev Neurosci. 1993;16:565–595. [Abstract] [Google Scholar]
- Sejersen T, Lendahl U. Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci. 1993 Dec;106(Pt 4):1291–1300. [Abstract] [Google Scholar]
- Sharp G, Osborn M, Weber K. Occurrence of two different intermediate filament proteins in the same filament in situ within a human glioma cell line. An immunoelectron microscopical study. Exp Cell Res. 1982 Oct;141(2):385–395. [Abstract] [Google Scholar]
- Sjöberg G, Jiang WQ, Ringertz NR, Lendahl U, Sejersen T. Colocalization of nestin and vimentin/desmin in skeletal muscle cells demonstrated by three-dimensional fluorescence digital imaging microscopy. Exp Cell Res. 1994 Oct;214(2):447–458. [Abstract] [Google Scholar]
- Sjöberg G, Edström L, Lendahl U, Sejersen T. Myofibers from Duchenne/Becker muscular dystrophy and myositis express the intermediate filament nestin. J Neuropathol Exp Neurol. 1994 Jul;53(4):416–423. [Abstract] [Google Scholar]
- Sotelo C, Alvarado-Mallart RM, Frain M, Vernet M. Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells. J Neurosci. 1994 Jan;14(1):124–133. [Europe PMC free article] [Abstract] [Google Scholar]
- Stemple DL, Anderson DJ. Isolation of a stem cell for neurons and glia from the mammalian neural crest. Cell. 1992 Dec 11;71(6):973–985. [Abstract] [Google Scholar]
- Tohyama T, Lee VM, Rorke LB, Marvin M, McKay RD, Trojanowski JQ. Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. Lab Invest. 1992 Mar;66(3):303–313. [Abstract] [Google Scholar]
- Tölle HG, Weber K, Osborn M. Microinjection of monoclonal antibodies to vimentin, desmin, and GFA in cells which contain more than one IF type. Exp Cell Res. 1986 Feb;162(2):462–474. [Abstract] [Google Scholar]
- Wood JN, Anderton BH. Monoclonal antibodies to mammalian neurofilaments. Biosci Rep. 1981 Mar;1(3):263–268. [Abstract] [Google Scholar]
- Zimmerman L, Parr B, Lendahl U, Cunningham M, McKay R, Gavin B, Mann J, Vassileva G, McMahon A. Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron. 1994 Jan;12(1):11–24. [Abstract] [Google Scholar]
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