[CTNF = Ciliary Neurotrophic Factor; FGF-2 = Fibroblast Growth Factor 2; OPC = Oligodendrocyte Progenitor Cell; MHV = Mouse Hepatitis Virus]
Neurobiol Dis. 2003 Jul;13(2):89-101
Albrecht PJ, Murtie JC, Ness JK, Redwine JM, Enterline JR, Armstrong RC, Levison SW.
Department of Neuroscience & Anatomy, Pennsylvania State University College of Medicine, 17033, Hershey, PA, USA
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.