| 1. |
- Ekström, Per A R, et al.
(författare)
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Leukemia inhibitory factor null mice : Unhampered in vitro outgrowth of sensory axons but reduced stimulatory potential by nerve segments
- 2000
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Ingår i: Neuroscience Letters. - 0304-3940. ; 281:2-3, s. 107-110
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Tidskriftsartikel (refereegranskat)abstract
- Leukemia inhibitory factor (LIF) is locally up-regulated after peripheral nerve injury and may be involved in the subsequent regeneration. Here, adult mice with or without LIF gene deletions were used to study the role of LIF in regeneration. The results show that axonal regeneration in vitro from dorsal root ganglia (DRGs) was unaffected by LIF deletion. However, segments from wild type mice promoted DRG axonal outgrowth better than segments from LIF deleted animals when in vivo-injured sciatic nerve segments were co-cultured with DRGs from normal adult mice. Addition of LIF could not restore the deficit. This suggests that LIF is engaged in the local regulation of regeneration but not in the regenerative events occuring at the cell body level. (C) 2000 Elsevier Science Ireland Ltd.
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| 2. |
- Sjögreen, B., et al.
(författare)
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Mitogen activated protein kinase inhibition by PD98059 blocks nerve growth factor stimulated axonal outgrowth from adult mouse dorsal root ganglia in vitro
- 2000
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Ingår i: Neuroscience. - 0306-4522. ; 100:2, s. 407-416
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'-methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by inhibiting its immediate upstream activator, mitogen activated protein kinase kinase (also known as MEK). Here we used PD98059 to study the role of mitogen activated protein kinase in the axonal outgrowth of adult dorsal root ganglia explants. Whereas PD98059 at 50μM left spontaneous axonal outgrowth unaffected, it markedly inhibited nerve growth factor stimulated axon growth when assessed after two days in culture. A mitogen activated protein kinase assay and immunoblotting using antibodies discriminating between activated and inactivated kinase, both confirmed that PD98059 reduced the amount of activated enzyme in nerve growth factor stimulated preparations, while the total amounts of the kinase remained unchanged. Immunohistochemistry revealed the presence of neuronal mitogen activated protein kinase kinase and mitogen activated protein kinase itself. The latter enzyme was found to be activated in the growing axons, as seen by whole-mount labelling. At the ganglionic level activated mitogen activated protein kinase was preferentially detected in satellite cells.The results show that nerve growth factor stimulated axonal outgrowth in vitro from adult mouse dorsal root ganglia utilizes the mitogen activated protein kinase pathway. Copyright (C) 2000 IBRO.
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| 3. |
- Wiklund, Peter, et al.
(författare)
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Axonal outgrowth from adult mouse nodose ganglia In vitro is stimulated by neurotrophin-4 in a Trk receptor and mitogen-activated protein kinase-dependent way
- 2000
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Ingår i: Journal of Neurobiology. - 0022-3034. ; 45:3, s. 142-151
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Tidskriftsartikel (refereegranskat)abstract
- The actions of neurotrophic factors on sensory neurons of the adult nodose ganglion were studied in vitro. The ganglia were explanted in an extracellular matrix-based gel that permitted observation of the growing axons. Neurotrophin-4 (NT-4) was a very efficient stimulator of outgrowth of axons from the nodose ganglion and had almost doubled the outgrowth length when this was analyzed after 2 days in culture. Brain-derived neurotrophic factor also stimulated outgrowth, but to a lesser degree, whereas NT-3 gave only weak stimulatory tendencies. Nerve growth factor and glial cell line-derived neurotrophic factor both lacked stimulatory effects. NT-4 is known to act via TrkB receptors, and the presence of these on growing nodose neurons was demonstrated immunohistochemically. In line with a Trk-mediated growth effect, the NT-4 stimulation was abolished by K252a, a selective inhibitor of neurotrophin receptor-associated tyrosine kinase activity. K252a had no effect on the unstimulated preparation. NT-4 treatment led to activation of the mitogen-activated protein kinase and inhibition of the latter pathway by PD98059 significantly reduced the NT-4 stimulated outgrowth, whereas the drug had no effect on the unstimulated growth. In conclusion, the data suggest that NT-4 can serve as a powerful growth factor for neurons of adult nodose ganglia and that the growth stimulation involves TrkB- and mitogen-activated protein kinase. (C) 2000 John Wiley and Sons, Inc.
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