TY - JOUR A1 - Sendtner, Michael A1 - Kreutzberg, Georg W. A1 - Thoenen, Hans T1 - Ciliary neurotrophic factor (CNTF) prevents the degeneration of motor neurons after axotomy N2 - 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. Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32637 ER - TY - RPRT A1 - Sendtner, Michael A1 - Kreutzberg, Georg W. A1 - Jennekens, Frans G. T1 - Workshop on trophic factors in the peripheral nervous system. Capri, October 1991. N2 - No abstract available Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31451 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 - Arakawa, Yoshihiro A1 - Stöckli, Kurt A. A1 - Kreutzberg, Georg W. A1 - Thoenen, Hans T1 - Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival N2 - We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities. CNTF is expressed selectively by Schwann cells and astrocytes of the peripheral and central nervous system, respectively, but not by target tissues of the great variety of CNTF -responsive neurons. CNTF mRNA is not detectable by Northern blot or PCR analysis during embryonic development and immediately after birth. However, during the second post-natal week, a more than 30-fold increase in CNTF mRNA and pro tein occurs in the sciatic nerve. Since the period of low CNTF levels in peripheral nerves coincides with that of high vulnerability of motoneurons (i.e. axonallesion results in degeneration of motoneuron cell bodies), insufficient availability of CNTF may be the reason for the rate of lesioninduced cell death of early post-natal motoneurons. Highly enriched embryonic chick motoneurons in culture are supported at survival rates higher than 60% by CNTF, even in single cell cultures, indicating that CNTF acts directly on motoneurons. In contrast to CNTF, the members of the neurotrophin gene family (NGF, BDNF and NT-3) do not support the survival of motoneurons in culture. However, aFGF and bFGF show distinct survival activities which are additive to those of CNTF, resulting in the survival of virtually all motoneurons cultured in the presence of CNTF and bFGF. KW - motoneurons KW - ciliary neurotrophic factor KW - CNTF KW - nerve lesion KW - rat KW - chick KW - neurotrophic factor Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-33048 ER - TY - JOUR A1 - Sendtner, Michael A1 - Stöckli, Kurt A. A1 - Carroll, Patrick A1 - Kreutzberg, Georg W. A1 - Thoenen, Hans T1 - More on motor neurons N2 - No abstract available Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42598 ER -