Skip to main content

Advertisement

SpringerLink
Log in

CNTF-Activated Astrocytes Release a Soluble Trophic Activity for Oligodendrocyte Progenitors

  • ORIGINAL PAPER
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

CNTF (ciliary neurotrophic factor) has been suggested to be an important survival factor for oligodendrocytes; however, this effect is inconsistently obtained and myelination appears normal in CNTF null animals. On the other hand, CNTF stimulates astrocytes to produce growth and trophic factors. Therefore, we tested the hypothesis that CNTF acts indirectly through astrocytes to promote oligodendrocyte survival. We show that CNTF-stimulated astrocytes release a trophic factor(s) that leads to more than double the number of oligodendrocyte progenitor cells (OPCs) by 48 h. The trophic activity fractionates at greater than 30 kD. By contrast, OPCs grown in CNTF supplemented chemically defined medium fared no better than cells grown without CNTF. Untreated astrocytes, and CNTF- and IL-1β -stimulated astrocytes all promoted the proliferation of OPCs to a similar extent, but only the CNTF-stimulated astrocyte conditioned media (CM) resulted in increased OPCs numbers. Cumulatively, these results confirm previous data indicating that astrocytes release potent mitogens for oligodendroglia, and demonstrate that CNTF stimulates astrocytes to release an OPC survival-promoting activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ness JK, Mitchell NE, Wood TL (2002) IGF-I and NT-3 signaling pathways in developing oligodendrocytes: differential regulation and activation of receptors and the downstream effector Akt. Dev Neurosci 24(5):437–445

    Article  PubMed  CAS  Google Scholar 

  2. Canoll PD, et al. (1996) GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Neuron 17:229–243

    Article  PubMed  CAS  Google Scholar 

  3. Gard AL, et al. (1995) Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia inhibitory factor-like protein. Development 121:2187–2197

    PubMed  CAS  Google Scholar 

  4. Grinspan JB, Franceschini B (1995) Platelet-derived growth factor is a survival factor for PSA-NCAM + oligodendrocyte pre-progenitor cells. J Neurosci Res 41:540–551

    Article  PubMed  CAS  Google Scholar 

  5. Barres BA, et al. (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70:31–46

    Article  PubMed  CAS  Google Scholar 

  6. Cui QL, Fogle E, Almazan G (2006) Muscarinic acetylcholine receptors mediate oligodendrocyte progenitor survival through Src-like tyrosine kinases and PI3K/Akt pathways. Neurochem Int 48(5):383–393

    Article  PubMed  CAS  Google Scholar 

  7. Li W, et al. (2004) Beneficial effect of erythropoietin on experimental allergic encephalomyelitis. Ann Neurol 56(6):767–77

    Article  PubMed  CAS  Google Scholar 

  8. Sattler MB, et al. (2004) Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis. Cell Death Differ 11(Suppl 2):S181–192

    Article  PubMed  Google Scholar 

  9. Colognato H, et al. (2004) Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. J Cell Biol 167(2):365–375

    Article  PubMed  CAS  Google Scholar 

  10. Molina-Holgado E, et al. (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22(22):9742–9753

    PubMed  CAS  Google Scholar 

  11. Jaillard C, et al. (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci 25(6):1459–1469

    Article  PubMed  CAS  Google Scholar 

  12. Shankar SL, et al, (2003) The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. J Neurosci 23(10):4208–4218

    PubMed  CAS  Google Scholar 

  13. Saini HS, et al. (2005) Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in oligodendrocyte progenitors. J. Neurochem 95(5):1298–1310

    Article  PubMed  CAS  Google Scholar 

  14. 2Nait-Oumesmar B, et al. (1999) Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci 11(12):4357–4366

    Article  Google Scholar 

  15. Vemuri GS, McMorris FA (1996) Oligodendrocytes and their precursors require phosphatidylinositol 3-kinase signaling for survival. Development 122:2529–2537

    PubMed  CAS  Google Scholar 

  16. Ness JK, Scaduto RC, Wood TL (2004) IGF-I prevents glutamate-mediated Bax translocation and cytochrome C release in O4 oligodendrocyte progenitors. Glia 46:183–194

    Article  PubMed  Google Scholar 

  17. Ness JK, Wood TL (2002) Insulin-like growth factor I, but not neurotrophin-3, sustains Akt activation and provides long-term protection of immature oligodendrocytes from glutamate-mediated apoptosis. Mol Cell Neurosci 20(3):476–488

    Article  PubMed  CAS  Google Scholar 

  18. Barres BA, et al. (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295

    PubMed  CAS  Google Scholar 

  19. Barres BA, et al. (1994) A crucial role for neurotrophin-3 in oligodendrocyte development. Nature 367:371–375

    Article  PubMed  CAS  Google Scholar 

  20. Louis JC, et al. (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259:689–692

    Article  PubMed  CAS  Google Scholar 

  21. Mayer M, Bhakoo K, Noble M (1994) Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. Development 120:143–153

    PubMed  CAS  Google Scholar 

  22. Kahn MA, de Vellis J (1994) Regulation of an oligodendrocyte progenitor cell line by the interleukin-6 family of cytokines. Glia 12:87–98

    Article  PubMed  CAS  Google Scholar 

  23. Barres BA, et al. (1996) Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation. Mol Cell Neurosci 8(2/3):146–156

    Article  CAS  Google Scholar 

  24. D’Souza SD, Alinauskas KA Antel JP (1996) Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. J Neurosci Res 43(3):289–298

    Article  PubMed  CAS  Google Scholar 

  25. DeChiara TM, et al. (1995) Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 83:313–322

    Article  PubMed  CAS  Google Scholar 

  26. Sendtner M, et al. (1994) Ciliary neurotrophic factor. J Neurobiol 25(11):1436–1453

    Article  PubMed  CAS  Google Scholar 

  27. Albrecht PJ, et al. (2002) Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival. Exp Neurol 173(1):46–62

    Article  PubMed  CAS  Google Scholar 

  28. Levison SW, McCarthy KD (1991) Astroglia in culture. In Banker GA, Goslin K (Eds) Culturing nerve cells. MIT press, Cambridge, p 309–336

    Google Scholar 

  29. Young GM, Levison SW (1997) An improved method for propagating oligodendrocyte progenitors in vitro. J Neurosci Meth 77:163–168

    Article  CAS  Google Scholar 

  30. Jiang F-J, Levison SW, Wood TL (1999) Ciliary neurotrophic factor induces expression of the IGF type 1 receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes. J Neurosci Res 57:447–457

    Article  PubMed  CAS  Google Scholar 

  31. Levison SW, et al. (2000) IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation. Glia 32(3):328–337

    Article  PubMed  CAS  Google Scholar 

  32. Albrecht PJ, et al. (2003) Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production. Neurobiol Dis 13(2):89–101

    Article  PubMed  CAS  Google Scholar 

  33. Noble M, Murray K (1984) Purified astrocytes promote the in vitro division of a bipotential glial progenitor cell. EMBO J 3:2243–2247

    PubMed  CAS  Google Scholar 

  34. Liberto CM, et al. (2004) Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89(5):1092–1100

    Article  PubMed  CAS  Google Scholar 

  35. Grinspan JB, et al. (1993) Trophic effects of basic fibroblast growth factor (bFGF) on differentiated oligodendroglia: a mechanism for regeneration of the oligodendroglial lineage. J Neurosci Res 36(6):672–680

    Article  PubMed  CAS  Google Scholar 

  36. Cohen RI, et al. (1996) Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes. J Neurosci 16(20):6433–6442

    PubMed  CAS  Google Scholar 

  37. Richardson WD, et al. (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53:309–319

    Article  PubMed  CAS  Google Scholar 

  38. Pinkas-Kramarski R, et al. (1994) Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes. Proc Natl Acad Sci USA 91(20):9387–9391

    Article  PubMed  CAS  Google Scholar 

  39. Gensert JM, Goldman JE (1997) Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19(1):197–203

    Article  PubMed  CAS  Google Scholar 

  40. Redwine JM, Armstrong RC (1998) In vivo proliferation of oligodendrocyte progenitors expressing PDGFalphaR during early remyelination. J Neurobiol 37(3):413–428

    Article  PubMed  CAS  Google Scholar 

  41. Prineas JW, et al. (1993) Multiple sclerosis: Remyelination of nascent lesions. Ann Neurol 33:137–151

    Article  PubMed  CAS  Google Scholar 

  42. Wolswijk G (2002) Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord. Brain 125(Pt 2):338–349

    Article  PubMed  Google Scholar 

  43. Chang A, et al. (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346(3):165–173

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Terri Wood for her help with the experiments and her constructive comments on this manuscript. This work was supported by a grant to SWL from the National Multiple Sclerosis Society, RG-2829.

Author information

Authors and Affiliations

  1. Center for Neuropharmacolgy and Neuroscience, Albany Medical Center, Albany, NY, 12208, USA

    Phillip J. Albrecht

  2. Pennsylvania State University College of Medicine, Hershey, PA, 17754, USA

    Jonathan C. Enterline

  3. Graduate Program in Neuroscience, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Jason Cromer

  4. Department of Neurology and Neuroscience, UMDNJ-New Jersey Medical School, 185 S. Orange Ave, East Orange, Newark, NJ, 07018-1095, USA

    Steven W. Levison

Authors
  1. Phillip J. Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan C. Enterline
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason Cromer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven W. Levison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven W. Levison.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Albrecht, P.J., Enterline, J.C., Cromer, J. et al. CNTF-Activated Astrocytes Release a Soluble Trophic Activity for Oligodendrocyte Progenitors. Neurochem Res 32, 263–271 (2007). https://doi.org/10.1007/s11064-006-9151-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-006-9151-6

Key words

Search

Navigation