Abstract
Nestin is an intermediate filament protein found in CNS progenitor cells. Nestin reappears in CNS tumor cells and reactive astrocytes after CNS injury. In this study we investigated whether nestin could be detected in the cerebrospinal fluid (CSF) of newborn infants and whether expression levels change with gestational age (GA) and/or brain injury. Using Western blot analysis, we examined the expression of nestin in the CSF of newborn infants(GA 25-42 wk) with asphyxia (n = 14), periventricular leukomalacia and peri(intra)ventricular hemorrhage (n = 7), and in a control group (n = 11). Protein extract from the periventricular brain tissue of a 1-wk-old infant was also analyzed. Nestin was detected in all the CSF samples and in the protein extract from the periventricular brain tissue. Although the CSF levels of nestin expression did not change with increasing GA, the asphyxia group had significantly lower levels of nestin in the CSF. An unexpected finding was that brain-derived nestin had an apparent molecular mass of approximately 240 kD, whereas all analyzed CSF samples contained two nestin-immunoreactive proteins at 200 and 220 kD. Experimental deglycosylation of the 240-kD form reduced the molecular mass to 220 kD, indicating that nestin undergoes a specific deglycosylation upon release into the CSF.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- CSF:
-
cerebrospinal fluid
- IF:
-
intermediate filament
- PVL:
-
periventricular leukomalacia
- PIVH:
-
peri(intra)ventricular hemorrhage
- GA:
-
gestational age
- PCR:
-
polymerase chain reaction
References
Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D 1994 Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13: 1071–1082
Morshead CM, van der Kooy D 1992 Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain. J Neurosci 12: 249–256
Lois C, Alvarez-Buylla A 1994 Long-distance neuronal migration in the adult mammalian brain. Science 264: 1145–1148
Reynolds BA, Weiss S 1992 Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255: 1707–1710
Lois C, Alvarez-Buylla A 1993 Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci USA 90: 2074–2077
Frederiksen K, McKay RDG 1988 Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci 8: 1144–1151
Lendahl U, Zimmerman LB, McKay RDG 1990 CNS stem cells express a new class of intermediate filament protein. Cell 60: 585–595
Fishell G, Mason CA, Hatten ME 1993 Dispersion of neural progenitors within the germinal zones of the forebrain. Nature 362: 636–638
Williams BP, Price J 1995 Evidence for multiple precursor cell types in the embryonic rat cerebral cortex. Neuron 14: 1181–1188
Dahlstrand J, Lardelli M, Lendahl U 1995 Nestin mRNR expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Dev Brain Res 84: 109–129
Dahlstrand J, Collins VP, Lendahl U 1992 Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res 52: 5334–5341
Tohyama T, Lee VM-Y, Rorke LB, Marvin M, McKay RDG, Trojanowsky JQ 1992 Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. Lab Invest 66: 303–313
Redies C, Lendahl U, McKay RDG 1991 Differentiation and heterogeneity in T-antigen immortalized precursor cell lines from mouse cerebellum. J Neurosci Res 30: 601–615
Clarke SR, Shetty AK, Bradley JL, Turner DA 1994 Reactive astrocytes express the embryonic intermediate neurofilament nestin. NeuroReport 5: 1885–1888
Lin RCS, Matesic DF, Marvin M, McKay RDG, Brustle O 1995 Reexpression of the intermediate filament nestin in reactive astrocytes. Neurobiol Dis 2: 79–85
Frisén J, Johansson CB, Török C, Risling M, Lendahl U 1995 Rapid, widespread and long-lasting induction of nestin contributes to the generation of glial scar tissue after CNS injury. J Cell Biol 131: 453–464
Zimmerman L, Lendahl U, Cunningham M, McKay R, Parr B, Gavin B, Mann J, Vassileva G, McMahon A 1994 Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12: 11–24
Sarnat HB, Sarnat MS 1976 Neonatal encephalopathy following fetal distress. Arch Neurol 33: 696–705
Dahlstrand J, Zimmerman LB, McKay RDG, Lendahl U 1992 Characterization of human nestin gene reveals a close evolutionary relationship to neurofilaments. J Cell Sci 103: 589–597
Löwenadler B, Jansson B, Paleus S, Holmgren E, Nilsson B, Moks T, Palm G, Josephson S, Philipson L, Uhlén M 1987 A gene fusion system for generating antibodies against short peptides. Gene 58: 87–97
Jin P, Farmer K, Ringertz N, Sejersen T 1993 Proliferation and differentiation of human fetal myoblasts is regulated by PDGF-BB. Differentiation 54: 47–54
Sejersen T, Lendahl U 1993 Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci 106: 1291–1300
Frederiksen K, Jat PS, Valtz N, Levy D, McKay R 1988 Immortalisation of precursor cells from the mammalian CNS. Neuron 1: 439–448
Heins S, Aebi U 1994 Making heads and tails of intermediate filament assembly, dynamics and networks. Curr Opin Cell Biol 6: 25–33
Nyberg F, Nordström K, Terenius L 1985 Endopeptidase in human cerebrospinal fluid which cleaves proenkephalin B opioid peptides at consecutive basic amino acids. Biochem Biophys Res Commun 131: 1069–1074
Acknowledgements
The authors thank Dr. Björn Löwenadler for generating the anti-nestin antiserum 4350, Hilary Brown for advise on Western blot analysis, Dr. Ron McKay and Dr. Tomas Sejersen for cells, Dr. Bronius Jurevicius for providing us with human brain tissue, and Dr. Giovanna Marchini for valuable comments on the manuscript.
Author information
Authors and Affiliations
Additional information
Supported by grants from Sahléns Stiftelse, the Swedish Medical Research Council 5234 (H.I.,) and 7164 (G.F.), the Swedish Cancer Society, Margaret och Axel Ax:son Johnsons Stiftelse, Kjell och Märta Beijers Stiftelse, Åke Wibergs Stiftelse and Magn. Bergvalls Stiftelse (U.L.), and ESPR Young Investigator Exchange Program (G.G.).
Rights and permissions
About this article
Cite this article
Grigelioniené, G., Blennow, M., Török, C. et al. Cerebrospinal Fluid of Newborn Infants Contains a Deglycosylated Form of the Intermediate Filament Nestin. Pediatr Res 40, 809–814 (1996). https://doi.org/10.1203/00006450-199612000-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199612000-00006
