Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival

Abstract

SummaryWe have demonstrated that the extensive degener ation of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities.

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

“…Similar positive effects have also been observed in vivo when CNTF was administered onto the chorioallantoic membrane of chick embryos at the same developmental stages (70,77). That CNTF has a direct action on motoneurons could be deduced from the fact that the survival effect in single motoneuron cultures was identical to that in 80% pure low-density cultures (94) . The cloning of CNTF was the prerequisite for producing large quantities of recombinant CNTF (49,59,100) and for the determination of its developmental expression and cellular localization (20,27,86,94,97,100,101).…”

“…The results obtained with this enriched preparation could later be confirmed by CNTF purified to homogeneity and recombinant CNTF (3,59,93,94).…”

“…For example, in contrast to the strong survival effects in vitro (both in chick and rat motoneuron cultures), both molecules were without protective effect against motoneuron degeneration after lesioning of the newborn rat facial nerve (39). The amounts of locally administered bFGF and FGF-5 corresponded to those of CNTF, BDNF, NT-3, NT-4, IGF-I, and LIF which showed a clear-cut, although differing, rescue effect (39,45,93,94). The limited amounts of available recombinant FGF -5 did not permit experiments with excessively high quantities of re comb inant FGF -5 as, for example, used for the demonstration of the protective effect of BDNF in the lesioned newborn rat sciatic nerve (107).…”

“…Further investigations demonstrated that CNTF had a much broader spectrum of action in vitro, including survival effects on sympathetic, sensory, and, more recently, hippocampal, locus coeruleus, and dopaminergic mesencephalic neurons (30,41,52,53,94) .…”

“…That CNTF has a direct action on motoneurons could be deduced from the fact that the survival effect in single motoneuron cultures was identical to that in 80% pure low-density cultures (94) . The cloning of CNTF was the prerequisite for producing large quantities of recombinant CNTF (49,59,100) and for the determination of its developmental expression and cellular localization (20,27,86,94,97,100,101). These investigations demonstrated that CNTF is expressed postnatally in myelinating Schwann cells (27,86,97,100,101) and a subpopulation of type I astrocytes (20,101) in the CNS, that CNTF is a cytosolic molecule, and that the biological activity, e.g., in the adult sciatic nerve, is more than 10,000 _ times higher than that of (retrogradely) transported NGF in the rat sciatic nerve (35,97,98).…”