RGD Reference Report - Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival. - Rat Genome Database

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Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival.

Authors: Albrecht, PJ  Dahl, JP  Stoltzfus, OK  Levenson, R  Levison, SW 
Citation: Albrecht PJ, etal., Exp Neurol. 2002 Jan;173(1):46-62.
RGD ID: 1626172
Pubmed: PMID:11771938   (View Abstract at PubMed)
DOI: DOI:10.1006/exnr.2001.7834   (Journal Full-text)

At focal CNS injury sites, several cytokines accumulate, including ciliary neurotrophic factor (CNTF) and interleukin-1beta (IL-1beta). Additionally, the CNTF alpha receptor is induced on astrocytes, establishing an autocrine/paracrine loop. How astrocyte function is altered as a result of CNTF stimulation remains incompletely characterized. Here, we demonstrate that direct injection of CNTF into the spinal cord increases GFAP expression and astroglial size and that primary cultures of spinal cord astrocytes treated with CNTF, IL-1beta, or leukemia inhibitory factor exhibit nuclear hypertrophy comparable to that observed in vivo. Using a coculture bioassay, we further demonstrate that CNTF treatment of astrocytes increases their ability to support ChAT(+) ventral spinal cord neurons (presumably motor neurons) more than twofold compared with untreated astrocytes. Also, the complexity of neurites was significantly increased in neurons cultured with CNTF-treated astrocytes compared with untreated astrocytes. RT-PCR analysis demonstrated that CNTF increased levels of FGF-2 and nerve growth factor (NGF) mRNA and that IL-1beta increased NGF and hepatocyte growth factor mRNA levels. Furthermore, both CNTF and IL-1beta stimulated the release of FGF-2 from cultured spinal cord astrocytes. These findings demonstrate that cytokine-activated astrocytes better support CNS neuron survival via the production of neurotrophic molecules. We also show that CNTF synergizes with FGF-2, but not epidermal growth factor, to promote DNA synthesis in spinal cord astrocyte cultures. The significance of these findings is discussed by presenting a new model depicting the sequential activation of astrocytes by cytokines and growth factors in the context of CNS injury and repair.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
astrocyte activation  IDA 1626172spinal cord astrocytesRGD 
positive regulation of cell growth  IDA 1626172spinal cord astrocytesRGD 
positive regulation of hormone secretion  IDA 1626172Fgf2 release from spinal cord astrocytesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cntf  (ciliary neurotrophic factor)


Additional Information