@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} } @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{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} }