Ciliary neurotrophic factor stimulates neurite outgrowth from spinal cord neurons

Abstract

Ciliary neurotrophic factor (CNTF) has been shown to promote the survival of motoneurons, but its effects on axonal outgrowth have not been examined in detail. Since nerve growth factor (NGF) promotes the outgrowth of neurites within the same populations of neurons that depend on NGF for survival, we investigated whether CNTF would stimulate neurite outgrowth from motoneurons in addition to enhancing their survival. We found that CNTF is a powerful promoter of neurite outgrowth from cultured chick embryo ventral spinal cord neurons. An effect of CNTF on neurite outgrowth was detectable within 7 hours, and at a concentration of 10 ng/ml, CNTF enhanced neurite length by about 3- to 4-fold within 48 hours. The neurite growth-promoting effect of CNTF does not appear to be a consequence of its survival-promoting effect. To determine whether the effect of CNTF on spinal cord neurons was specific for motoneurons, we analyzed cell survival and neurite outgrowth for motoneurons labeled with diI, as well as for neurons taken from the dorsal half of the spinal cord, which lacks motoneurons. We found that the effect of CNTF was about the same for motoneurons as it was for neurons from the dorsal spinal cord. The responsiveness of a variety of spinal cord neurons to CNTF may broaden the appeal of CNTF as a candidate for the treatment of spinal cord injury or disease.

Focal application of neutralizing antibodies to soluble neurotrophic factors reduces collateral axonal branching after peripheral nerve lesion

“…The ciliary neurotrophic factor (CNTF) increases the rate of axonal elongation, axonal sprouting, number of re‐innervated muscle end‐plates and improves functional recovery (Gurney et al ., 1992; Curtis et al ., 1993; Sahenk et al ., 1994; Ulenkate et al ., 1994; Newman et al ., 1996; Oyesiku & Wigston, 1996). Treatment with 100 µg/mL anti‐CNTF (group C 11 ) decreased the number of double‐labelled neurons when compared to the mouse IgG control, but not vs. the other controls (Table 2).…”

Intraocular Gene Transfer of Ciliary Neurotrophic Factor Prevents Death and Increases Responsiveness of Rod Photoreceptors in theretinal degeneration slowmouse

“…However, because rds/peripherin appears essential for the elaboration of the membranal disks composing normal ROS (Travis et al, 1992;Kedzierski et al, 1997) and the segments of the CNTFtreated rds/rds retina are still shorter and more disorganized than that of a wild-type retina, it appears unlikely that the CNTF treatment could have corrected the defect in the stabilization of ROS disks associated with this rds/peripherin null mutant. Because C N TF displays neurite-promoting activity on some neuronal populations (Bianchi and Cohan, 1993;C arri et al, 1994;Oyesiku and Wigston, 1996;Syed et al, 1996;Guo et al, 1997), a more parsimonious hypothesis would be that, by stimulating synthesis of membranous material, the C N TF treatment could have shifted the balance between the rate of generation of abortive ROS membranes and the rate of their shedding, leading to accumulation of these ROS membranes. The increase in density and size of rom-1-positive structures decorating photoreceptor segments that is seen after C N TF treatment could, thus, be the result of an accelerated enlargement of the short, rom-1-positive, vesicular expansions normally found on a subset of photoreceptor segments in the rds/rds retina (Jansen and Sanyal, 1984;Nir and Papermaster, 1986; see also Fig.…”

Neural Tissue Engineering: Strategies for Repair and Regeneration

“…CNTF promotes motor neuron survival (202,203), outgrowth (204), and sprouting (205). CNTF is thought to play a role in the response of spinal cord to injury, as CNTF mRNA is found at increased levels adjacent to spinal cord lesions (206).…”