Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production.
Multiple sclerosis is characterized by multiple lesions with selective loss of myelin and oligodendrocytes, leading to deficits of sensation and movement, as well as cognitive disabilities. Consequently, a major research endeavor is to identify strategies to enhance oligodendrocyte regeneration and remyelination. FGF-2 is a potent mitogen for OPCs, and it is induced in astrocytes in animal models of demyelinating diseases in conjunction with successful remyelination. However, the factors responsible for inducing FGF-2 after demyelination in astrocytes are unknown. Here we show that CNTF mRNA and protein increase coincident with spinal cord remyelination in mice recovering from MHV-induced demyelination. We identify CNTF within astrocytes surrounding and within remyelinating lesions, and show that CNTF increases FGF-2 ligand and receptor mRNAs in spinal cord after direct application. Furthermore, we show that CNTF increases FGF-2 mRNA approximately 2.5-fold in cultured mouse spinal cord astrocytes. Altogether, these results strongly implicate CNTF as an important cytokine in demyelinating disease and as an upstream regulator of FGF-2 production in astrocytes during early remyelination.
Albrecht
Phillip J
PJ
Department of Neuroscience & Anatomy, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Murtie
Joshua C
JC
Ness
Jennifer K
JK
Redwine
Jeffrey M
JM
Enterline
Jonathan R
JR
Armstrong
Regina C
RC
Levison
Steven W
SW
D018759:Adrenergic Uptake Inhibitors / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D018929:Cell Culture Techniques; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D013566:Sympathomimetics / Q000378:metabolism; D013997:Time Factors; D014439:Tyramine / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D020934:Ciliary Neurotrophic Factor; C496460:Fgf9 protein, mouse; C496461:Fgf9 protein, rat; D051525:Fibroblast Growth Factor 9; D007375:Interleukin-1; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D013566:Sympathomimetics; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496350:Fgfr1 protein, rat; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D014439:Tyramine