TY  - JOUR
A1  - Sendtner, Michael
A1  - Dittrich, F.
A1  - Hughes, R. A.
A1  - Thoenen, H.
T1  - Actions of CNTF and neurotrophins on degenerating motoneurons : preclinical studies and clinical implications
N2  - Spinal motoneurons innervating skeletal muscle were amongst the first neurons shown to require the presence of their target cells to develop appropriately. Isolated embryonie chick and rat motoneurons have been used to identify neurotrophic factors and cytokines capable of supporting the survival of developing motoneurons. Such factors include ciliary neurotrophic factor (CNTF), which is present physiologically in high amounts in myelinating Schwann cells of peripheral nerves, and brain-derived neurotrophic factor (BDNF) which is synthesized in skeletal muscle and, after peripheral nerve lesion. in Schwann cells. These factors have been further analyzed for their physiological significance in maintaining motoneuron function in vivo, and for their potential therapeutic usefulness in degenerative motoneuron disease. Both CNTF and BDNF are capable of rescuing injured facial motoneurons in newbom rats. Furthermore, CNTF prolongs survival and improves motor function of pmn mice, an animal model for degenerative motoneuron disease, by preventing degeneration of motoneuron axons and somata. Thus treatment of human motoneuron disease with neurotrophic factors should be possible, provided that rational means for application of these factors can be established considering also the appearance of potential side effects.
KW  - Neurobiologie
KW  - Motor neuron disease; Ciliary neurotrophic factor; Brain-derived neurotrophic factor; Animal models; Neurotrophic factors
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62939
ER  - 
TY  - JOUR
A1  - Sendtner, Michael
A1  - Carroll, P.
A1  - Holtmann, B
A1  - Hughes, R. A.
A1  - Thoenen, H.
T1  - Ciliary Neurotrophic Factor
N2  - No abstract available
KW  - ciliary neuron
KW  - ciliary neurotrophic factor
KW  - motoneuron
KW  - nonneuronaI cells
KW  - homologous recombination
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42545
ER  - 
TY  - JOUR
A1  - Sendtner, Michael
A1  - Stöckli, Kurt A.
A1  - Thoenen, Hans
A1  - Schmalbruch, H.
A1  - Carroll, P.
A1  - Kreutzberg, Georg W.
T1  - Ciliary neurotrophic factor prevents the degeneration of motor neurons in mouse mutant progressive motor neuronopathy
N2  - 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.
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42563
ER  - 
TY  - JOUR
A1  - Sendtner, Michael
A1  - Gnahn, H.
A1  - Wakade, A.
A1  - Thoenen, Hans
T1  - Is activation of the Na\(^+\)K\(^+\) pump necessary for NGF-mediated neuronal survival?
N2  - The ability of nerve growth factor to cause rapid activation of the Na+K+ pump of its responsive cells was examined by measuring the uptake of 86Rb+. A significant increase in 86Rb+ uptake in Ea chick dorsal root ganglion sensory neurons after NGF treatment was seen only if the cells had been damaged during the preparation procedure. Such damaged cells could not survive in culture in the presence of NGF, and undamaged cells that did survive in response to NGF exhibited no increased 86Rb+ uptake rate. Furthermore, cultured calf adrenal medullary cells did not show an increase in 86Rb+ uptake after treatment with NGF, although these cells respond to NGF with an increased synthesis of catecholaminergic enzymes. These results are incompatible with the hypothesis that the mechanism of action of NGF that promotes neuronal survival and enzyme induction results from an initial stimulation of the Na+K+ pump.
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42610
ER  -