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At least 19 recordsLinked to original sources
PubMed1999

Alterations in expression of the neurotrophic factors glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophic factor, in the target-deprived olfactory neuroepithelium.

Neuronal growth factors play an important role in the development and maintenance of the nervous system. In the olfactory system, neurogenesis and synapse formation occur not only during development but throughout life and it would be expected that growth factors play a significant role in these ongoing processes. We have examined the expression of three neurotrophic factors, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophic factor in the normal rat olfactory system and following synaptic target ablation (olfactory bulbectomy). We found that brain-derived neurotrophic factor immunoreactivity was confined to the horizontal basal cells of the olfactory neuroepithelium and was unaltered by bulbectomy. Glial cell line-derived neurotrophic factor immunoreactivity was present in the mature olfactory neurons and also their synaptic target cells in the olfactory bulb. Following bulbectomy, glial cell line-derived neurotrophic factor immunoreactivity was abolished from the neuroepithelium. Ciliary neurotrophic factor was present throughout the olfactory neuronal lineage with strongest immunoreactivity in the horizontal basal cells and mature olfactory neurons as well as several cell types in the olfactory bulb. Postbulbectomy, there was loss of strong ciliary neurotrophic factor immunoreactivity in olfactory neurons, however, low levels persisted in the remaining neuronal population. Horizontal basal cell immunoreactivity persisted over three months. Our results would be consistent with glial cell line-derived neurotrophic factor expression in mature olfactory neurons being dependent upon functional synaptic contact with the olfactory bulb. Alternatively, this factor may be acting as target-derived growth factor for olfactory neurons, a role in keeping with its function in spinal motoneurons and in the nigrostriatal system. Brain-derived neurotrophic factor is implicated in the trophic support of immature neurons. Ciliary neurotrophic factor is clearly important in this unique neuronal system but elucidation of its role awaits further investigation.

Animals↗
PubMed1994

Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor.

PURPOSE: The protective effects of three survival-promoting agents on ischemia-induced retinal injury in the rat were investigated. The agents included brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF). METHODS: Retinal ischemia was induced in Lewis albino rats by increasing intraocular pressure to 160 mm Hg for 90 minutes. The agents or buffer controls were injected intravitreally at different times, either before or after the ischemic insult, and the postischemic survival time was either 7 or 14 days. The degree of retinal damage was assessed from plastic-embedded sections by cytologic analysis, measurement of the thickness of several layers, and neuronal counts of the ganglion cell layer. RESULTS: Retinal ischemia thinned and reduced cell numbers in the inner retinal layers, but not in the photoreceptor nuclear layer. Each agent transiently ameliorated the degenerative changes when it was injected 2 days before ischemia. At 7 days postischemia, the inner retinal layers were far less damaged, and more ganglion cells were present than in buffer-injected or uninjected eyes. The protective effect was no longer evident at 14 days postischemia, except in the inner nuclear layer of the BDNF-treated eyes. If a second injection of BDNF was made 5 days after the ischemic insult, then the inner retinal layers were more preserved than buffer controls at 14 days postischemia, but the survival of ganglion cells was not enhanced. A single injection of BDNF at either 1 or 3 days postischemia reduced the degree of inner retinal damage and increased the number of surviving ganglion cells over that in buffer-injected controls. (CNTF and bFGF were not studied with postischemic injections.) CONCLUSIONS: BDNF, CNTF, and bFGF transiently protect the retina from pressure-induced ischemic injury when given 2 days before ischemia, and a second injection of BDNF given postischemically can prolong the protective effect. Moreover, protection afforded by BDNF can be seen even when applied only 1 or 3 days after the ischemic insult, although the protective effect is greater at 1 day than at 3 days postischemia.

Animals↗
PubMed1991

Cloning and expression of human ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a survival factor for avian ciliary ganglion neurons and a variety of other neuronal cell types in vitro. We report here the cloning of the entire genomic sequence encoding human CNTF and its primary structure. Biologically active CNTF has been expressed in Chinese hamster ovary cells from a human genomic DNA clone. Human CNTF has no significant sequence similarity to any previously reported protein, although approximately 84% similarity exists compared with rat and rabbit CNTF. The lack of both an N-terminal signal sequence and consensus sequences for glycosylation or hydrophobic regions, and the fact that active CNTF is expressed but not released into the culture medium of transfected cells, argue in favour of human CNTF as a cytosolic protein. These data provide a basis for understanding the role of CNTF in nervous system physiology and pathology.

Amino Acid Sequence↗
PubMedDate not supplied

Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) was originally characterized as a survival factor for chick ciliary neurons in vitro. More recently, it was shown to promote the survival of a variety of other neuronal cell types and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR). In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT). This increase is paralleled by a reduction of tyrosine hydroxylase (TH) activity. Moreover, CNTF promotes the differentiation of bipotential 02A progenitor cells to type-2-astrocytes in vitro. To help establish which, if any, of these functions CNTF exerts in vivo, it is necessary to determine its primary structure, cellular expression, developmental regulation and localization. The complementary DNA-deduced amino-acid sequence and subsequent expression of cDNA clones covering the entire coding region in HeLa-cells indicate that CNTF is a cytosolic protein. This, together with its regional distribution and its developmental expression, show that CNTF is not a target-derived neurotrophic factor. CNTF thus seems to exhibit neurotrophic and differentiation properties only after becoming available either by cellular lesion or by an unknown release mechanism.

Amino Acid Sequence↗
PubMed1993

Characterisation of high-affinity and low-affinity receptors for ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) supports the survival of a wide variety of neuronal cells in culture. To characterise the receptor(s) mediating the biological responses of CNTF we measured the binding of radiolabelled CNTF to chick sympathetic neurons and human neuroblastoma cells. Two distinct CNTF-binding sites with high and low affinity for the ligand were identified by steady-state binding experiments. Furthermore, two low-affinity binding sites could be discriminated on the basis of the dissociation rates. Cross-linking experiments showed that CNTF interacts with two proteins, one of 80 kDa and one of 140 kDa. The identity of the 80-kDa protein was determined by transient transfection experiments with the rat CNTF-binding protein CNTFR alpha while the properties of the 140-kDa protein correspond to those of gp130. Antisense experiments confirmed that CNTFR alpha is necessary for high affinity binding of 125I-CNTF and therefore a necessary subunit of the high-affinity receptor.

Animals↗
PubMed1994

Structure-function studies of human ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a polypeptide that promotes the survival and/or differentiation of a number of neural cell types. Here we present a structural and functional analysis of the human CNTF molecule. Variant proteins were synthesized by Escherichia coli transformed with mutant cDNA constructs, and purified by SDS-polyacrylamide gel electrophoresis and reverse phase high pressure liquid chromatography. Most variant CNTF proteins lacked neurotrophic activity, but two N- and C-terminal deletions (delta 2-14 and delta 173-200, respectively) actually displayed a several-fold increase in specific activity. Loss of biological activity was accompanied by changes in the alpha-helical nature of CNTF as measured by circular dichroism. These data strengthen the proposed similarity between CNTF and the family of hematopoietic cytokines.

Animals↗
PubMed1995

Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) has recently been found to share receptor components with, and to be structurally related to, a family of broadly acting cytokines, including interleukin-6, leukemia inhibitory factor, and oncostatin M. However, the CNTF receptor complex also includes a CNTF-specific component known as CNTF receptor alpha (CNTFR alpha). Here we describe the molecular cloning of the human and mouse genes encoding CNTFR. We report that the human and mouse genes have an identical intron-exon structure that correlates well with the domain structure of CNTFR alpha. That is, the signal peptide and the immunoglobulin-like domain are each encoded by single exons, the cytokine receptor-like domain is distributed among 4 exons, and the C-terminal glycosyl phosphatidylinositol recognition domain is encoded by the final coding exon. The position of the introns within the cytokine receptor-like domain corresponds to those found in other members of the cytokine receptor superfamily. Confirming a recent study using radiation hybrids, we have also mapped the human CNTFR gene to chromosome band 9p13 and the mouse gene to a syntenic region of chromosome 4.

Amino Acid Sequence↗
PubMed1995

Preparation and a structure-function analysis of human ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a trophic protein that promotes survival and/or differentiation of a variety of neuronal cell types including sensory, sympathetic, and motor neurons. CNTF, leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and oncostatin M (OSM) share a predicted common helical framework and partially identical receptor components. In this study, we present the preparation and structure--functional analysis of recombinant human CNTF. The human CNTF gene was expressed under the control of the PL promoter in Escherichia coli, and the mutants were constructed by insertion, deletion and site-directed mutagenesis. The recombinant proteins were purified from bacteria via DEAE A-50 and Sephacryl S-200 chromatography, and their survival promoting activities were determined using cultures of embryonic chick dorsal root ganglion (DRG) neurons. Insertion at position 23 with APGL, or at position 79 with PRGA, or substitution of 162L163Q for PIDG resulted in proteins with no neurotrophic activity. However, insertion at position 186 with PRGI did not alter human CNTF activity. Deletion of the carboxy-terminal amino acid 186-200 did not reduce the biological activity, but elimination of the amino acid 162-186 abolished the activity. The mutant substituting of 17 Cys for Ser was found to display a biological activity equivalent to that of the wild type. Our data provided experimental confirmation for the structural prediction of CNTF.

Amino Acid Sequence↗
PubMed1991

Sequence and structural organization of the human gene encoding ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a potent polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes survival, neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. We have cloned the gene encoding human CNTF (hCNTF) and have characterized its structure and organization. The hCNTF gene appears to be a unique-copy gene with a simple genetic organization, since only a single intron interrupts the coding domain. The hCNTF gene is located on chromosome 11, as determined using human-hamster somatic cell hybrids. The CNTF protein is highly conserved in evolution. The amino acid (aa) sequences of rat and rabbit CNTF translated from cDNAs display approx. 85% homology with the deduced aa sequence encoding hCNTF.

Amino Acid Sequence↗
PubMed1994

Ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) was first identified and partially purified from embryonic chick eye tissues. Subsequently, it was shown that CNTF is also present in large amounts in sciatic nerves of adult rats and rabbits, which led to its final purification and cloning. CNTF is not secreted by the classical secretory pathway involving the endoplasmatic reticulum and Golgi complex, but can be detected in high quantities within the cytoplasm of myelinating Schwann cells and astrocytes using immunohistochemistry. CNTF supports survival and/or differentiation of a variety of neuronal cell types including sensory, sympathetic, and motoneurons. Also, nonneuronal cells, such as oligodendrocytes, microglial cells, liver cells, and skeletal muscle cells, respond to exogenously administered CNTF, both in vitro and in vivo. During development, expression of CNTF is very low, if indeed it is expressed at all, and the phenotype of mice lacking endogenous CNTF after inactivation of the CNTF gene by homologous recombination suggests that CNTF does not play a crucial role for responsive cells during embryonic development. However, motoneurons are lost postnatally in mice lacking endogenous CNTF, suggesting that CNTF acts physiologically on the maintenance of these cells. The ability of exogenous CNTF to protect against motoneuron loss following lesion or in other animal models indicates that CNTF might be useful in the treatment of human motoneuron disorders, provided appropriate means of administration can be found.

Amino Acid Sequence↗
PubMed1999

Activation of SOCS-3 messenger ribonucleic acid in the hypothalamus by ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a neurocytokine expressed in glial cells that acts on brain cells to promote gene expression, survival, and differentiation. When administered systemically, CNTF reduces food intake and body weight in rodents. Genes encoding suppressors of cytokine signaling (SOCS) are induced by cytokines that activate membrane receptors in the same class as those that are activated by CNTF. We therefore examined the ability of CNTF to induce expression of socs genes in brain and peripheral tissues of rats and mice. Peripheral CNTF administration to ob/ob mice rapidly induced SOCS-3 messenger RNA (mRNA) in hypothalamus, as determined by Northern blotting and quantitative RT-PCR, but had no effect on cytokine-inducible sequence (CIS), SOCS-1, or SOCS-2 mRNA. In situ hybridization histochemistry of hypothalamus from ob/ob mice and normal rats demonstrated that CNTF induced SOCS-3 mRNA in the arcuate nucleus (Arc). Strong hybridization signals were also detected in the ependymal lining of the ventricles and the subfornical organ. This hybridization pattern was distinct from that resulting from peripheral leptin treatment with overlapping hybridization patterns only in the Arc. CNTF also induced expression of CIS, SOCS-1, SOCS-2, and SOCS-3 mRNA in the liver, and SOCS-2 and SOCS-3 mRNA in the kidney. CNTF induced SOCS-3 mRNA and SOCS-3 protein levels in an astrocyte cell line. Transient expression of SOCS-3, but not CIS or SOCS-2, inhibited CNTF-induced signal transduction in astrocytes. In conclusion, SOCS-3 mRNA is specifically induced by CNTF in regions of the hypothalamus that are both overlapping and distinct from that induced by leptin. Similar to leptin, the Arc is likely to be a direct target of CNTF, and this region may play a role in the body weight-reducing effects of CNTF. SOCS-3 is a negative regulator of CNTF signal transduction, and inhibitors of SOCS-3 function may enhance endogenous CNTF signaling after neuronal injury or enhance the body weight-reducing effect of CNTF after peripheral administration.

Animals↗
PubMed1998

Repair with collagen tubules linked with brain-derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model.

OBJECTIVE: To determine if brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) can be successfully delivered to transected and repaired peripheral nerves by cross-linking the factors to collagen tubules (CTs). METHODS: Forty-eight Sprague-Dawley rats underwent left sciatic nerve transection and repair. In the control group, CTs were implanted with no neurotrophic ligand (n=13). There were 3 experimental groups: CT with BDNF covalently linked to the collagen matrix (CT/BDNF; n=12), CT with CNTF covalently linked (CT/CNTF; n=12), and CT with both BDNF and CNTF covalently linked (CT/BDNF/CNTF; n=11). Functional outcome of neural regeneration was assessed every 10 days using walking track analysis, which was submitted to a sciatic functional index. Nerve morphometry, electrophysiologic studies, and molecular analysis for neural proteins were performed at the completion of the study at postoperative day 90. RESULTS: Animals in all 3 experimental groups achieved significantly superior maximal functional recovery, larger nerve cross-sectional areas, and a greater number of axons when compared with the control CT group (P<.001, P<.05, and P<.05, respectively). The animals in the CT/BDNF/CNTF group displayed the best functional recovery and had the largest axon diameters, greatest amplitude, and the fastest nerve conduction velocities. Molecular analysis revealed significant differences in the expression of neurofilament, neural cell adhesion molecule, myelin-associated glycoprotein, and myelin basic protein. CONCLUSIONS: We present the first evidence that CNTF covalently linked to CTs can improve functional recovery compared with CTs alone. We also support the previous finding that BDNF covalently linked to CTs significantly increases the functional recovery of transected and repaired nerves. Finally, we found that cotreatment produced the best functional recovery in our model.

Animals↗
PubMed1996

Synaptic modulation by neurotrophic factors: differential and synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor.

Extracellular application of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) to developing neuromuscular junctions in Xenopus nerve-muscle cultures resulted in an increase in the frequency of spontaneous synaptic currents (SSCs) and in the amplitude of nerve-evoked synaptic currents. Analyses of the amplitude and time course of the SSCs suggest that these effects are attributable to elevation of presynaptic transmitter release. The actions of these two factors on the transmitter secretion process, however, are distinctly different. Fura-2 Ca2+ imaging showed that an increase in presynaptic cytosolic Ca2+ ([Ca2+]i) accompanied the synaptic potentiation by BDNF, whereas no change in [Ca2+]i was observed during synaptic potentiation by CNTF. Removing external Ca2+ also abolished the potentiating effect of BDNF but did not influence the CNTF effect. Moreover, the two factors exerted different effects on the short-term synaptic plasticity. Paired-pulse facilitation normally found at these synapses was reduced by BDNF but unaffected by CNTF; CNTF, but not BDNF, reduced the extent of synaptic depression during high-frequency tetanic stimulation. Finally, the potentiation effect of BDNF and CNTF on spontaneous transmitter release was additive when both factors were applied together to the synapse at saturating concentrations (100 ng/ml) and was highly synergistic when low doses (1 and 10 ng/ml) of both factors were used. These results suggest that because of their differential effects on the secretory machinery, BDNF and CNTF may act cooperatively in modulating the development and functioning of synapses.

Animals↗
PubMed1994

Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons.

Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy-induced reduction in transmitter markers [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE) in neonatal or adult animals or the axotomy-induced up-regulation of the low-affinity neurotrophin receptor p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75NGFR in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype.

Acetylcholinesterase↗
PubMed1999

Synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, and ciliary neurotrophic factor (CNTF), a member of the neurocytokine family, are known to have synergistic effects on motoneurons, but such synergistic effect has not been studied in detail especially in the brain. In the present study, we examined the synergistic effects of BDNF and CNTF on the survival of basal forebrain cholinergic neurons cultured from postnatal 2-week-old (P2w) rats. Although BDNF is well-known to promote the survival of basal forebrain cholinergic neurons in P2w culture, CNTF had little effect on the survival of choline acetyltransferase (ChAT)-positive neurons and did not increase ChAT activity in the culture. However, CNTF enhanced BDNF-mediated promotion of cell survival of cholinergic neurons when added concomitantly. BDNF alone induced only a three-fold increase in ChAT activity in control cultures, but the concomitant addition of CNTF resulted in an eight-fold increase. CNTF did not enhance BDNF-mediated cell survival of total neurons from the basal forebrain, hippocampus or cerebellum, suggesting that the synergistic effects of CNTF on the BDNF-mediated increase of viability might be strong in basal forebrain cholinergic neurons. CNTF also enhanced the neurotrophin-4/5-mediated increase of ChAT activity, but not the nerve growth factor (NGF)-mediated one. Furthermore, the BDNF-mediated increase was also enhanced by leukemia inhibitory factor but not by interleukin-6. Similar synergistic pattern between neurotrophins and cytokines were also observed in the induction of ChAT activity in embryonic basal forebrain culture. These results suggest that TrkB, a functional high-affinity receptor of BDNF and NT-4/5, and LIFR beta, a receptor component contained in CNTF and LIF receptor complex, might be involved in the observed synergistic effects.

Acetylcholine↗
PubMed1994

The effect of nerve growth factor, ciliary neurotrophic factor, and ACTH analogs on cisplatin neurotoxicity in vitro.

Cisplatin, used to treat ovarian, bladder, and testicular cancers, causes a sensory dose-limiting neuropathy. Preliminary observations in humans and animals suggest that nerve damage may be prevented by ACTH analogs, particularly those belonging to the melanocortin class, and by nerve growth factor (NGF). We established a rat embryo dorsal root ganglion model to study cisplatin neurotoxicity. The drug reproducibly inhibited axonal growth at concentrations similar to that known to produce toxicity in neurons. The inhibition was prevented in a dose-dependent fashion by simultaneous exposure to alpha-melanocyte stimulating hormone (alpha-MSH) or ACTH but not by excess NGF or ciliary neurotrophic factor (CNTF). The ACTH peptides were not effective in preventing suramin-induced neurotoxicity in the same model. Drug interaction and dose-response studies showed that ACTH and alpha-MSH do not act by potentiation of NGF action. ACTH analogs appear to protect against cisplatin-induced neurotoxicity directly at the cellular level.

Adrenocorticotropic Hormone↗
PubMed1987

Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines--the mouse C 1300 N2a and the human IMR 32--mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 micrograms (IMR 32) and 140 micrograms (C 1300 N2a) of protein per ml and saturable at plateau values for surviving neurons identical to those achieved with purified CNTF. Small amounts of a CNTF-like material are also detectable in medium conditioned by NB cells. The activity is destroyed by heat and trypsin and not blocked by antibodies to (mouse) nerve growth factor. Unlike the neurite-promoting and neuronal-survival modulating agent laminin, it cannot be depleted on poly(L-alpha-ornithine)-coated plastic surfaces. NB IMR 32 cell extracts were electrophoresed using NaDodSO4/PAGE and transferred to nitrocellulose. Ciliary ganglion neurons seeded on the blotting paper in culture medium lacking CNTF ("cell blot") exclusively survive on two distinct bands with apparent molecular masses of 24 and 48 kDa. Twenty-four kilodaltons is the molecular mass of a CNTF purified from rat sciatic nerve. These results suggest that NB cells may contain a CNTF-like protein and provide further evidence that neurons may store neurotrophic factors. Purified (chicken) CNTF failed to affect proliferation and neurite growth of NB cells. The biological relevance of CNTF for NB cells, therefore, remains to be elucidated.

Animals↗
PubMed1997

Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons.

The neurotrophic factors ciliary neurotrophic factor and brain-derived neurotrophic factor can prevent motor neuron cell death during development and after nerve lesion in neonatal rodents. However, local and systemic application of these factors to newborn rats with damaged motor nerves rescues motor neurons only transiently during the first two weeks after axotomy. In order to test the effect of continuous delivery of these factors, the effect of localized injection of CNTF- or BDNF-transducing recombinant adenoviruses into the lesioned nerves was investigated. Under such conditions, survival of axotomized motor neurons is maintained for at least 5 weeks. This way of delivery corresponds to the physiological situation in adult rodents, under which endogenous CNTF is present in the cytosol of Schwann cells and BDNF expression is upregulated after nerve lesion, making these factors available to the damaged motor neurons. Recent results show that overexpression of muscle-derived neurotrophin-3 prevents degeneration of axons and motor endplates, but has only little effect on the number of motor neuron cell bodies in a murine animal model of motor neuron disease. Therefore, techniques suitable for tonic exposure to both nerve- and muscle-derived neurotrophic factors may have implications for the design of future therapeutic strategies against human motor neuron disease.

Adenoviridae↗