Cholinergic growth factor from skeletal muscle elevated following denervation.
ABSTRACT The effect of skeletal muscle extracts upon cholinergic neuron in vitro survival was investigated. All muscle soluble protein extracts elicited survival of neurons above that of neurons alone in culture and were found to be active below a protein concentration of 1.0 mg/ml. However, skeletal muscle which had been previously denervated, was found to contain higher amounts of survival activity than innervated muscle extracts. This elevation of survival activity was greatest within the first 7 days post-denervation, but subsequently declined towards the innervated level.
- SourceAvailable from: Martin Raff[Show abstract] [Hide abstract]
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.The Journal of Cell Biology 11/1991; 115(2):447-59. · 9.69 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The normal embryonic development of spinal cord motoneurons (MNs) involves the proliferation of precursor cells followed by the degeneration of approximately 50% of postmitotic MNs during the period when nerve-muscle connections are being established. The death of MNs in vivo can be ameliorated by activity blockade and by treatment with muscle extracts. Muscle activity and innervation have been suggested to regulate the availability of putative muscle-derived neurotrophic agent(s), and MNs are thought to compete for limited amounts of these trophic agents during normal development. Thus, activity and innervation are thought to regulate MN survival by modulating trophic factor availability. We have tested this notion by examining MN survival in vivo and ChAT development in spinal cord neurons in vitro following treatments with partially purified muscle extracts from normally active, paralyzed (genetically or pharmacologically), aneural, denervated, slow tonic, and fast-twitch muscles from embryonic and postnatal animals. Extracts from active and chronically inactive embryonic avian and mouse muscles were found to be equally effective in promoting the in vivo survival of MNs in the chick embryo. Similarly, extracts from fast-twitch and slow tonic postnatal avian muscles did not differ in their ability to promote both MN survival in vivo and ChAT activity in vitro. Although aneural and control embryonic muscle extract had similar effects on ChAT development in vitro, aneural muscle extract contained somewhat less MN survival-promoting activity when tested in vivo. By contrast, denervated postnatal muscle extract was more effective in promoting both MN survival in vivo and ChAT activity in vitro than age-matched control muscle extract.(ABSTRACT TRUNCATED AT 250 WORDS)The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/1991; 11(9):2829-37. · 6.75 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Ciliaryneurotrophicfactor(CNTF) isa po- tentsurvivalmoleculefora varietyofembryonic neu- ronsinculture.The developmentalexpressionof CNTF occursclearlyafterthetimeperiodofthe physiologicalcelldeathofCNTF-responsive neurons. This,togetherwiththesitesof expression,excludes CNTF as a target-derived neuronalsurvivalfactor,at leastinrodents.However, CNTF alsoparticipates in theinductionoftype2 astrocytedifferentiation invi- tro.Here we demonstratethatthetimecourseofthe expressionof CNTF-mRNA and protein:intheratop- ticnerve (asevaluatedby quantitative Northernblot analysisand biologicalactivity,, respectively) iscompa- tiblewithsucha glialdifferentiation functionofCNTF