@article{CarrollSendtnerMeyeretal.1993,
  author    = {Carroll, Patrick and Sendtner, Michael and Meyer, Michael and Thoenen, Hans},
  title     = {Rat ciliary neurothrophic factor (CNTF): gene structure and regulation of mRNA levels in glial cell cultures.},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31763},
  year      = {1993},
  abstract  = {The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyteenriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-gamma. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed.},
  language  = {en}
}
@article{SendtnerKreutzbergThoenen1990,
  author    = {Sendtner, Michael and Kreutzberg, Georg W. and Thoenen, Hans},
  title     = {Ciliary neurotrophic factor (CNTF) prevents the degeneration of motor neurons after axotomy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32637},
  year      = {1990},
  abstract  = {The period of natural cell death in the development of rodent motor neurons is followed by a period of sensitivity to axonal injury1-3. In the rat this early postnatal period of vulnerability coincides with that of very low ciliary neurotrophic factor (CNTF) levels in the sciatic nerve before CNTF increases to the high, adult levels4. The developmental time course of CNTF expression, its regional tissue distribution and its cytosolic localization (as suggested by its primary structure)4*5 favour a role for CNTF as a lesion factor rather than a target-derived neurotrophic molecule like nerve growth factor. Nevertheless CNTF exhibits neurotrophic activity in vitro on different populations of embryonic neurons6. To determine whether the vulnerability of motor neurons to axotomy in the early postnatal phase is due to insufficient availability of CNTF, we transected the axons of newborn rat motor neurons and demonstrated that iocal application of CNTF prevents the degeneration of the corresponding cell bodies.},
  language  = {en}
}
@article{StoeckliLottspeichSendtneretal.1989,
  author    = {St{\"o}ckli, K. A. and Lottspeich, F. and Sendtner, Michael and Masiakowski, P. and Carroll, Patrick and G{\"o}tz, Rudolf and Lindholm, D. and Thoenen, Hans},
  title     = {Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34229},
  year      = {1989},
  abstract  = {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 otherneuronal cell types and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of yasoactiYe intestinal peptide immunoreactiyity (VIP-IR). In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT.},
  language  = {en}
}
@article{MasuWolfHoltmannetal.1993,
  author    = {Masu, Yasuo and Wolf, Eckhard and Holtmann, Bettina and Sendtner, Michael and Brem, Gottfried and Thoenen, Hans},
  title     = {Disruption of the CNTF gene results in motor neuron degeneration},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33038},
  year      = {1993},
  abstract  = {CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a subpopulation of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.},
  language  = {en}
}
@article{StoeckliLililienNaeherNoeetal.1991,
  author    = {St{\"o}ckli, K. A. and Lililien, L. E. and N{\"a}her- No{\´e}, M. and Breitfeld, G. and Hughes, Richard A. and Raff, M. C. and Thoenen, Hans and Sendtner, Michael},
  title     = {Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31172},
  year      = {1991},
  abstract  = {Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a variety of embryonic neurons in culture. The developmental expression of CNTF occurs clearly after the time period of the physiological cell death of CNTF-responsive neurons. This, together with the sites of expression, excludes CNTF as a target-derived neuronal survival factor, at least in rodents. However, CNTF also participates in the induction of type 2 astrocyte differentiation in vitro. Here we demonstrate that the time course of the expression of CNTF-mRNA and protein in the rat optic nerve (as evaluated by quantitative Northern blot analysis and biological activity, respectively) is compatible with such a glial differentiation function of CNTF in vivo. We also show that the type 2 astrocyte-inducing- activity previously demonstrated in optic nerve extract can be precipitated by an antiserum against CNTF. Immunohistochemical analysis of astrocytes in vitro and in vivo demonstrates that the expression of CNTF is confined to a subpopulation of type 1 astrocytes. The olfactory bulb of adult rats has comparably high levels of CNTF to the optic nerve, and here again, CNTF-immunoreactivity is localized in a subpopulation of astrocytes. However, the postnatal expression of CNTF in the olfactory bulb occurs later than in the optic nerve. In other brain regions both CNTF-mRNA and protein levels are much lower.},
  language  = {en}
}
@article{SendtnerStoeckliThoenen1992,
  author    = {Sendtner, Michael and St{\"o}ckli, K. A. and Thoenen, Hans},
  title     = {Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31738},
  year      = {1992},
  abstract  = {Ciliary neurotrophic factor (CNTF) is expressed in high quantities in Schwann cells of peripheral nerves during postnatal development of the rat. The absence of a hydrophobic leader sequence and the immunohistochemical localization of CNTF within the cytoplasm of these cells indicate that the factor might not be available to responsive neurons under physiological conditions. However, CNTF supports the survival of a variety of embryonic neurons, including spinal motoneurons in culture. Moreover we have recently demonstrated that the exogenous application of CNTF protein to the lesioned facial nerve of the newborn rat rescued these motoneurons from cell death. These results indicate that CNTF might indeed play a major role in assisting the survival of lesioned neurons in the adult peripheral nervous system. Here we demonstrate that the CNTF mRNA and protein levels and the manner in which they are regulated are compatible with such a function in lesioned peripheral neurons. In particular, immunohistochemical analysis showed significant quantities of CNTF at extracellular sites after sciatic nerve lesion. Western blots and determination of CNTF biological activity of the same nerve segments indicate that extracellular CNTF seems to be biologically active. After nerve lesion CNTF mRNA levels were reduced to <5 \% in distal regions of the sciatic nerve whereas CNTF bioactivity decreased to only one third of the original before-lesion levels. A gradual reincrease in Schwann cells occurred concomitant with regeneration.},
  language  = {en}
}
@misc{ThoenenHughesSendtner1993,
  author    = {Thoenen, Hans and Hughes, Richard A. and Sendtner, Michael},
  title     = {Trophic support of motoneurons: physiological, pathophysiological, and therapeutic implications.},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31746},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}
@article{ArakawaSendtnerThoenen1990,
  author    = {Arakawa, Yoshihiro and Sendtner, Michael and Thoenen, Hans},
  title     = {Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31718},
  year      = {1990},
  abstract  = {No abstract available},
  language  = {en}
}
@article{SendtnerStoeckliThoenenetal.1992,
  author    = {Sendtner, Michael and St{\"o}ckli, Kurt A. and Thoenen, Hans and Schmalbruch, H. and Carroll, P. and Kreutzberg, Georg W.},
  title     = {Ciliary neurotrophic factor prevents the degeneration of motor neurons in mouse mutant progressive motor neuronopathy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42563},
  year      = {1992},
  abstract  = {CILIARY neurotrophic factor (CNTF) supports the survival of embryonic motor neurons in vitro and in vivo and prevents lesion-mediated degeneration of rat motor neuron~ during early post-natal stages. Here we report that CNTF greatly reduces all the functional and morphological changes in pmnlpmn mice5, an autosomal recessive mutant leading to progressive caudo-cranial motor neuron degeneration. The first manifestations of progressive motor neuronopathy in homozygous pmnl pmn mice become apparent in the hind limbs at the end of the third post-natal week and all the mice die up to 6 or 7 weeks after birth from respiratory paralysis. Treatment with CNTF prolongs- survival- and greatly Impoves motor function of these mice. Moreover, morphological manifestations, such as loss of motor axons in the phrenic nerve and degeneration of facial motor neurons, were greatly reduced by CNTF, although the treatment did not start until the first symptoms of the disease had already become apparent and substantial degenerative changes were already present. The protective and restorative effects of CNTF in this mouse mutant give new perspectives for the treatment of human degenerative motor neuron diseases with CNTF.},
  language  = {en}
}
@article{HughesSendtnerGoldfarbetal.1993,
  author    = {Hughes, Richard A. and Sendtner, Michael and Goldfarb, Mitchell and Lindholm, Dan and Thoenen, Hans},
  title     = {Evidence that fibroblast growth factor 5 is a major muscle-derived survival factor for cultured spinal motoneurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42588},
  year      = {1993},
  abstract  = {We examined the potential role of fibroblast growth factor 5 (FGF-5) as a target-derived trophic factor for spinal motoneurons. Northern analysis of total RNA from rat skeletal muscle revealed an FGF-5 mRNA transcript both during the period of embryonic motoneuron death and in the adult. Recombinant human FGF-5 supported the survival of highly enriched cultures of embryonic chick motoneurons. Significant proportions of the motoneuron survival activity of rat skeletal muscle extracts could be immunoprecipitated using an antiserum to FGF-5. The immunoprecipitable activity was present in soluble and matrix-bound forms in embryonic muscle, but bound exclusively to the extracellular matrix in adult muscle. These results, along with the secretory nature of FGF-5, suggest that FGF-5 may act as a target-derived trophic factor for motoneurons.},
  language  = {en}
}