@article{GoetzKoesterWinkleretal.1994,
  author    = {G{\"o}tz, Rudolf and K{\"o}ster, Reinhard and Winkler, Christoph and Raulf, Friedrich and Lottspeich, Friedrich and Schartl, Manfred and Thoenen, Hans},
  title     = {Neurotrophin-6 is a new member of the nerve growth factor family},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61544},
  year      = {1994},
  abstract  = {DURING vertebrale development, many neurons depend for survival and differentiation on their target cells\(^{1-3}\). The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)\(^1\). NGF and the other known members of tbe neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT -3) and neurotrophin-4/5 (NT -4/5) are conserved as distinct genes over large evolutionary distances\(^{4 -6}\). Here we report the cloning of neurotrophin-6 (NT -6), a new member of this family from the teleost fish Xiphophorus. NT -6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT -6 from cell surface and extracellular matrix molecules. Recombinant purified NT -6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT -6 is expressed in tbe embryonie valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecuJes may modulate its action in the nervous system .},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SendtnerThoenen1994,
  author    = {Sendtner, Michael and Thoenen, Hans},
  title     = {Oxidative stress and motorneuron disease},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42684},
  year      = {1994},
  abstract  = {Transgenic mice carrying mutated Cu/Zn superoxide dismutase genes provide insights into the pathogenesis of human motorneuron diseases and may be useful as models in the development and testing of therapies.},
  language  = {en}
}
@article{DittrichThoenenSendtner1994,
  author    = {Dittrich, Falk and Thoenen, Hans and Sendtner, Michael},
  title     = {Ciliary neurotrophic factor: pharmacokinetics and acute-phase response in rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42639},
  year      = {1994},
  abstract  = {No abstract available},
  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}
}
@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{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{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}
}
@incollection{ThoenenHughesSendtner1993,
  author    = {Thoenen, Hans and Hughes, Richard A. and Sendtner, Michael},
  title     = {Towards a comprehensive understanding of the trophic support of motoneurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31117},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1993},
  abstract  = {Motoneurons played an essential role in establishing the concept of target-mediated support of innervating neurons. However, it took several decades until molecules were identined which trophically support motoneurons in vitro and in vivo. The most potent molecule identined so far is ciliary neurotrophic factor (CNTF). It is expressed as a cytosolic molecule in myelinating Schwann cells rather than in skeletal muscle in the postnatal period and therefore does not qualify as a target-derived neurotrophic factor regulating motoneuron survival during embryonic development. However, the inactivation of CNTF by gene targeting experiments results in progressive atrophy and degeneration of motoneurons, demonstrating that CNTF plays an essential role as a maintenance factor for motoneurons postnatally. Secretory molecules which are expressed in skeletal muscle during embryonic development and which support motoneurons in culture and partially also in vivo include members of the NGF gene family (BDNF, NT-3, NT-4/S) , FGF-S, IGF-I, and UF. The evaluation of the physiological importance of these molecules is under investigation.},
  language  = {en}
}
@article{SendtnerThoenenHughes1993,
  author    = {Sendtner, Michael and Thoenen, Hans and Hughes, R. A.},
  title     = {Members of several gene families influence survival of rat motoneurons in vitro and in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42652},
  year      = {1993},
  abstract  = {The survival and functional maintenance of spinal motoneurons, both during the period of developmental cell death and in adulthood, have been shown to be dependent on trophic factors. In vitro experiments have previously been used to identify several survival factors for motoneurons, including CNTF, UF, and members of the neurotrophin, FGF, and IGF gene families. Some of these factors have also been shown to be active in vivo, either on chick motoneurons during embryonic development or on lesioned facial and spinal motoneurons of the newborn rat. Here we demonstrate that lesioned newborn rat facial motoneurons can be rescued by NT-4/5, IGF-I, and UF. Furthermore, in contrast to chick motoneurons, the survival of isolated embryonic rat motoneurons can be maintained by the neurotrophins BDNF, NT-3, and NT-4/5. IGF-I and FGF-5 were also active in this system, each supporting more than 50\% of the originally plated neurons. The responsiveness of motoneurons to multiple factors in vitro and in vivo suggests that motoneuron survival and function are regulated by the coordinated actions of members of different gene families.},
  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}
}