Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes

Rick I. Cohen, Ronen Marmur, William T. Norton, Mark F. Mehler, John A. Kessler

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

There is increasing evidence that the neurotrophins, particularly nerve growth factor (NGF) and neurotrophin-3 (NT-3), play a role in the regulation of glial development in the CONS. Recent studies have shown that the proliferation of optic nerve-derived O2A progenitors (OLPs) is potentiated by NT-3 in combination with platelet-derived growth factor, whereas NT-3 alone supports the survival of their differentiated progeny (Barres et al., 1994). In this study, we have examined the expression of the high affinity neurotrophin receptors (trks) and the low-affinity nerve growth factor receptor p75 in developing oligodendrocytes (OLs). In addition, we have examined the effects of NGF and NT-3 on proliferation end survival of OLPs and OLs, respectively. TrkC, the high-affinity NT-3 receptor, and trKA, the high-affinity NGF receptor, are both expressed from the early OLP through the mature OL stage. The truncated form of trkB, lacking the tyrosine kinase domain, and the low-affinity neurotrophin receptor p75 are expressed at low levels in OLPs and are upregulated in mature OLs. NGF and NT-3 both induced the phosphorylation of mitogen-activated protein kinase (MAPK) in OLPs and in OLs. In both OLPs and OLs, NT-3 sustained the activation of MAPK more than NGF. NT-3 enhanced the proliferation of OLPs and supported the survival of OLs. By contrast, unless coadministered with FGF-2, NGF did not exhibit mitogenic effects on OLPs but did enhance the survival of differentiated OLs. Our data demonstrate the presence of functional trkA and trkC in developing OLs and indicate that both NGF and NT-3 have a broad spectrum of developmental actions on cells of the OL lineage.

Original languageEnglish (US)
Pages (from-to)6433-6442
Number of pages10
JournalJournal of Neuroscience
Volume16
Issue number20
StatePublished - Oct 15 1996

Fingerprint

Neurotrophin 3
Oligodendroglia
Nerve Growth Factor
Brain
Nerve Growth Factor Receptor
Mitogen-Activated Protein Kinases
trkC Receptor
Nerve Growth Factor Receptors
Platelet-Derived Growth Factor
Nerve Growth Factors
Fibroblast Growth Factor 2
Cell Lineage
Optic Nerve
Neuroglia
Protein-Tyrosine Kinases
Phosphorylation

Keywords

  • MAP kinase
  • neurotrophins
  • oligodendrocytes
  • p75
  • proliferation
  • survival
  • trks

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes. / Cohen, Rick I.; Marmur, Ronen; Norton, William T.; Mehler, Mark F.; Kessler, John A.

In: Journal of Neuroscience, Vol. 16, No. 20, 15.10.1996, p. 6433-6442.

Research output: Contribution to journalArticle

Cohen, Rick I. ; Marmur, Ronen ; Norton, William T. ; Mehler, Mark F. ; Kessler, John A. / Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 20. pp. 6433-6442.
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