Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum

Asada, Hideo; Ip, Nancy Y.; Li, Pan; Razack, N.; Parfitt, Margaret M.; Plunkett, Robert J.

doi:10.1002/jnr.490400104

Cited by 68 publications

(35 citation statements)

References 35 publications

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“…But it has not been determined which ligand is most relevant during normal development, nor have studies elucidated which ligands are important for the expansion of NSPs after injury (which we probably need not emphasize is likely a more complex process than maintenance). Many studies on injuries to the adult brain have shown that CNTF is dramatically increased (Ip et al, 1993,Asada et al, 1995,Herx et al, 2000,Albrecht et al, 2003. Based on these data we hypothesized that CNTF would increase after neonatal H/I whereupon it would signal through its cognate receptor to effect expansion of the NSPs in the SVZ.…”

Section: Discussionmentioning

confidence: 94%

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

Covey

Levison

2007

Neuroscience

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Subsequent to perinatal hypoxia/ischemia there is an increase in the number of neural stem/progenitor cells (NSP) within the subventricular zone. Gene expression analyses have implicated Notch signaling in the expansion of these tripotential cells but there are limited data as to which signals are stimulating Notch activation. There is evidence that the LIFR/gp130 receptor heterodimer induces Notch1 to maintain NSP populations during normal development. LIF and CNTF bind to these receptor components and they coordinate injury responses in the CNS. Therefore, the aim of these studies was to investigate whether CNTF and/or LIF participate in NSP expansion in the SVZ after H/I as well as to characterize the downstream events that regulate NSP numbers. We report that LIF mRNA is induced 48 hours post insult by 13 fold but that it returns almost to baseline by 72 hours. Commensurate with increased LIF expression there is a corresponding increase in phosphorylated STAT-3 within the SVZ. Modeling the changes that occur in vivo, we show that LIF induces STAT-3 phosphorylation in neurospheres to enhance Delta-like-1 and Notch1 expression as well as to increase Notch1 activation. LIF also expands neurosphere number and size in vitro. Whereas CNTF can mimic the effects of LIF in vitro, CNTF expression in the SVZ was unchanged during recovery from H/I. Cumulatively, these data implicate LIF and not CNTF in the expansion of NSPs in the SVZ after perinatal brain injury. As both LIF expression and the endogenous regenerative response after brain injury are time-delimited, these findings provide insights into strategies to expand the endogenous pool of NSPs to repopulate the damaged brain.

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Section: Discussionmentioning

confidence: 94%

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

Covey

Levison

2007

Neuroscience

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“…Neurotrophic factors are produced around the locus of CNS lesions, and although earlier studies did not identify the source of these factors (NietoSampedro et al, 1982(NietoSampedro et al, , 1983Needels et al, 1986;Ernfors et al, 1989;Ishikawa et al, 1991;Lindvall et al, 1994), more recent studies have documented the upregulation of nerve growth factor (NGF) (Bakhit et al, 1991;Altar et al, 1992;Oderfeld-Nowak et al, 1992;Arendt et al, 1995), ciliary neurotrophic factor (Ip et al, 1993;Asada et al, 1995;Wen et al, 1995), basic fibroblast growth factor (Finklestein et al, 1988;Frautschy et al, 1991;GomezPinilla et al, 1995;Wen et al, 1995), and insulin-like growth factor-1 (Komoly et al, 1992) in reactive astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

et al. 1997

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The relevance of astrogliosis remains controversial, especially with respect to the beneficial or detrimental influence of reactive astrocytes on CNS recovery. This dichotomy can be resolved if the mediators of astrogliosis are identified. We have measured the levels of transcripts encoding inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α, which are considered to be microglia/macrophage cytokines. The elevations preceded, or occurred concomitantly with, the rise in glial fibrillary acidic protein mRNA, an early manifestation of astrogliosis. In neonatal mice, IL-1 and TNF-α mRNA were elevated to a greater extent by an NC-implant injury, which produced astrogliosis, than after an NC-stab, with minimal astrogliosis. We determined whether endogenous interferon (IFN)-γ could be responsible for the observed increases in IL-1 and TNF-α, because IFN-γ is a potent microglia/macrophage activator, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-γ was demonstrated by three lines of evidence. First, no increase in IFN-γ transcripts could be found at injury. Second, the administration of a neutralizing antibody to IFN-γ did not attenuate astrogliosis. Third, in IFN-γ knockout adult mice, astrogliosis and increases in levels of IL-1α and TNF-α were induced rapidly by injury. The marked elevation of inflammatory cytokines is discussed in the context of astrogliosis and general CNS recovery.

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“…Expression of both CNTF and its receptor, the CNTFR␣, are induced following injury to the central nervous system (CNS; Ip et al, 1993;Rudge et al, 1994;Asada et al, 1995;Oyesiku et al, 1997). Moreover, CNTF protein accumulates in wound cavities (Nieto-Sampedro et al, 1982;Asada et al, 1996) and is elevated in the cerebral spinal fluid (CSF) of patients with acute multiple sclerosis (MS ;Massaro, 1998).…”

Section: Introductionmentioning

confidence: 99%

Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes

Jiang¹,

Levison²,

Wood³

1999

J. Neurosci. Res.

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Ciliary neurotrophic factor (CNTF) is produced and released in response to injury in the central nervous system (CNS). While CNTF initially was characterized as a trophic factor for neurons, more recent evidence supports roles for this factor in survival, proliferation, and maturation of oligodendrocyte lineage cells. Evidence is emerging to support the hypothesis that CNTF's actions may include enhancing other growth and trophic factors. Here we tested the hypothesis that CNTF can induce expression of receptors on oligodendrocytes for factors that are known to promote their generation, maturation, and survival. Specifically, we used an in vivo paradigm to test whether CNTF, when injected stereotactically into forebrain white matter of adult rats, could induce mRNA expression for the insulin-like growth factor (IGF) type I receptor (IGF-IR), fibroblast growth factor (FGF) receptor (FGFR)-1, FGFR3, and platelet-derived growth factor (PDGF) receptor-alpha (PDGFRalpha). We determined that CNTF injection increased expression of IGF-IR and FGFR1 mRNAs in adult white matter to 200-250% of control levels. Cellular analysis indicated that these receptor mRNAs were induced in interfascicular oligodendrocytes. In contrast, CNTF had no effect on levels of FGFR3 and PDGFRalpha mRNAs. These results suggest that CNTF enhances the sensitivity of oligodendrocytes to other mitogens and trophic factors via induction of their receptors.

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Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum

Cited by 68 publications

References 35 publications

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes

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