Co-administration of ciliary neurotrophic factor with its soluble receptor protects against neuronal death and enhances neurite outgrowth.
Attempts to promote neuronal survival and repair with ciliary neurotrophic factor (CNTF) have met with limited success. The variability of results obtained with CNTF may, in part, reflect the fact that some of the biological actions of the cytokine are mediated by a complex formed between CNTF and its specific receptor, CNTFRalpha, which exists in both membrane-bound and soluble forms. In this study, we compared the actions of CNTF alone and CNTF complexed with soluble CNTFRalpha (hereafter termed "Complex") on neuronal survival and growth. Although CNTF alone produced limited effects, Complex protected against glutamate-mediated excitotoxicity via gap junction-dependent and -independent mechanisms. Further examination revealed that only Complex promoted neurite outgrowth. Differential gene expression analysis revealed that, compared with CNTF alone, Complex differentially regulates several neuroprotective and neurotrophic genes. Collectively, these findings indicate that CNTF exerts more robust effects on neuronal survival and growth when applied in combination with its soluble receptor.
Ozog
Mark A
MA
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Modha
Geetanjalee
G
Church
John
J
Reilly
Rayne
R
Naus
Christian C
CC
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; D046912:Multiprotein Complexes