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P.g.h. Clarke - One of the best experts on this subject based on the ideXlab platform.
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Competitive exclusion between axons dependent on a single Trophic Substance: a mathematical analysis.
Bellman Prize in Mathematical Biosciences, 1996Co-Authors: N. Jeanprêtre, P.g.h. Clarke, J.-p. GabrielAbstract:A mathematical model is presented of competition between axons for a Trophic Substance, such as is believed to occur particularly during development. The model is biologically realistic. The growth-stimulating activity of the Trophic molecules is assumed to result from their binding to high-affinity receptors on neurons and their axons, but the model also incorporates uptake by nonneuronal cells possessing only lower affinity receptors. Plausible and fairly general assumptions are made concerning the kinetics of binding and internalization and the effects on axonal growth. The model takes into account the possibility that Trophic factor production may be regulated by the afferent axons or autoregulated. The variables specified are the "axonal vigor" of each axon, representing the ability of each axon to take up Trophic molecules, and the concentration of Trophic molecules in the extracellular space of the axonal target region. Of the several parameters introduced, the most important turns out to be the "zero vigor-growth parameter," which is defined as the concentration of Trophic molecules that gives zero growth of the vigor of a given axon. By means of a Lyapunov function, it is shown that the system will approach asymptotically to a stable equilibrium characterized by the survival of only the axon whose zero-growth parameter is lowest. Or, if several axons share the same lowest zero-growth parameter, these will all survive. The model may be particularly relevant to the elimination of polyneuronal innervation from developing muscle fibers and from autonomic ganglion cells.
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Timing of neuronal death following successive blockade of protein synthesis and axoplasmic transport in the axonal target territory.
Developmental Neuroscience, 1992Co-Authors: P.f. Blaser, P.g.h. ClarkeAbstract:Neurons in the isthmo-optic nucleus (ION) of chick embryos can withstand a substantial cycloheximide-induced reduction in protein synthesis in their target territory, the retina, at the very time when their survival is known to depend on a retrograde signal from the latter. We here test the hypothesis that this resistance to the cycloheximide injection might be due to the accumulation in the ION of a reserve of retina-derived Trophic molecules (or of resulting second messengers). Following an intraocular injection of cycloheximide at E15 to deplete the hypothetical reserve in one ION, both eyes received injections of colchicine (which blocks axoplasmic transport) at E16. The resulting time course of cell death was very similar in the two IONs, which refutes the hypothesis. The most plausible alternative is that there is a reserve of Trophic Substance in the retina capable of maintaining the ION for about 1 day.
Jeffrey H. Kordower - One of the best experts on this subject based on the ideXlab platform.
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p75 nerve growth factor receptor immunoreactivity in the human brainstem and spinal cord.
Brain research, 1992Co-Authors: Elliott J. Mufson, Thomas Brashers-krug, Jeffrey H. KordowerAbstract:The distribution of nerve growth factor receptor (NGFR) immunoreactive profiles was investigated in the adult human brainstem and spinal cord using a monoclonal antibody directed against the primate low affinity (p75) NGFR. In the human brainstem, p75NGFR immunoreactive profiles were seen within the mesencephalic and descending nucleus of the trigeminal nerve, the nucleus and tractus solitarius, glossopharyngeal nerve, hypoglossal nucleus, nucleus subtrigeminalis, subnucleus ventralis of the central nucleus of the medulla, nucleus cuneatus and gracilis. At the level of the upper cervical spinal cord, p75NGFR immunoreactive profiles were also seen within the incoming dorsal roots, zone of Lissauer and substantia gelatanosa (lamina II). Virtually no immunoreactivity was associated with cervical spinal cord motor neurons. The demonstration of the p75NGFR in brainstem and spinal cord regions associated with the central transmission of peripheral sensory information suggests that these systems may be influenced by the Trophic Substance nerve growth factor.
Elliott J. Mufson - One of the best experts on this subject based on the ideXlab platform.
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p75 nerve growth factor receptor immunoreactivity in the human brainstem and spinal cord.
Brain research, 1992Co-Authors: Elliott J. Mufson, Thomas Brashers-krug, Jeffrey H. KordowerAbstract:The distribution of nerve growth factor receptor (NGFR) immunoreactive profiles was investigated in the adult human brainstem and spinal cord using a monoclonal antibody directed against the primate low affinity (p75) NGFR. In the human brainstem, p75NGFR immunoreactive profiles were seen within the mesencephalic and descending nucleus of the trigeminal nerve, the nucleus and tractus solitarius, glossopharyngeal nerve, hypoglossal nucleus, nucleus subtrigeminalis, subnucleus ventralis of the central nucleus of the medulla, nucleus cuneatus and gracilis. At the level of the upper cervical spinal cord, p75NGFR immunoreactive profiles were also seen within the incoming dorsal roots, zone of Lissauer and substantia gelatanosa (lamina II). Virtually no immunoreactivity was associated with cervical spinal cord motor neurons. The demonstration of the p75NGFR in brainstem and spinal cord regions associated with the central transmission of peripheral sensory information suggests that these systems may be influenced by the Trophic Substance nerve growth factor.
A. Saria - One of the best experts on this subject based on the ideXlab platform.
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Secretoneurin promotes pertussis toxin‐sensitive neurite outgrowth in cerebellar granule cells
Journal of neurochemistry, 2003Co-Authors: M. C. Gasser, I. Berti, Kurt F. Hauser, Reiner Fischer-colbrie, A. SariaAbstract:The neuropeptide secretoneurin (SN) is an endoproteolytic product of the chromogranin secretogranin II. We investigated the effects of SN on the differentiation of immature cerebellar granule cells derived from the external granular layer (EGL). Secretoneurin caused concentration-dependent increases in neurite outgrowth, reflecting differentiation. The maximum effect was reached at a concentration of 100 nM SN. Secretoneurin immunoneutralization using specific antiserum significantly decreased neurite outgrowth; however, neurite morphology was altered. An affinity chromatography-purified antibody significantly inhibited the outgrowth response to SN ( p < 0.001) without altering the morphology. Binding studies suggest the existence of specific G-protein-coupled receptors on the surface of monocytes that recognize SN. Assuming that SN promotes neurite outgrowth in EGL cells by acting through a similar G-protein-coupled mechanism, we treated SN-stimulated EGL cultures with pertussis toxin. Exposure to pertussis toxin (0.1 lg/mL) showed a significant inhibition of the SN-induced outgrowth. To establish a second messenger pathway we used the protein kinase C inhibitor staurosporine. We found that EGL cell viability was not enhanced following chronic SN treatment for 24 h. These data indicate that SN is a novel Trophic Substance that can affect cerebellar maturation, primarily by accelerating granule cell differentiation through a signalling mechanism that is coupled to pertussis toxin-sensitive G-proteins.
Thomas Brashers-krug - One of the best experts on this subject based on the ideXlab platform.
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p75 nerve growth factor receptor immunoreactivity in the human brainstem and spinal cord.
Brain research, 1992Co-Authors: Elliott J. Mufson, Thomas Brashers-krug, Jeffrey H. KordowerAbstract:The distribution of nerve growth factor receptor (NGFR) immunoreactive profiles was investigated in the adult human brainstem and spinal cord using a monoclonal antibody directed against the primate low affinity (p75) NGFR. In the human brainstem, p75NGFR immunoreactive profiles were seen within the mesencephalic and descending nucleus of the trigeminal nerve, the nucleus and tractus solitarius, glossopharyngeal nerve, hypoglossal nucleus, nucleus subtrigeminalis, subnucleus ventralis of the central nucleus of the medulla, nucleus cuneatus and gracilis. At the level of the upper cervical spinal cord, p75NGFR immunoreactive profiles were also seen within the incoming dorsal roots, zone of Lissauer and substantia gelatanosa (lamina II). Virtually no immunoreactivity was associated with cervical spinal cord motor neurons. The demonstration of the p75NGFR in brainstem and spinal cord regions associated with the central transmission of peripheral sensory information suggests that these systems may be influenced by the Trophic Substance nerve growth factor.