Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures

Kimpinski, Kurt; Campenot, Robert B.; Mearow, Karen M.

doi:10.1002/(sici)1097-4695(199710)33:4<395::aid-neu5>3.0.co;2-5

Cited by 106 publications

(68 citation statements)

References 46 publications

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“…Unlike those in the embryo, adult DRG neurons are neurotrophin independent and do not require NGF for survival (Lindsay, 1988, Lindsay and Harmar, 1989, Kimpinski et al, 1997, Winston et al, 2001, Dodge et al, 2002. Further, the absence of serum restricts glial proliferation, and allows the assay of specific ligand stimulation.…”

Section: Discussionmentioning

confidence: 99%

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

Hall

2007

Neuroscience

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Calcitonin Gene-Related Peptide (CGRP) increases in sensory neurons after inflammation and plays an important role in abnormal pain responses, but how this neuropeptide is regulated is not well understood. Both activin A and Nerve Growth Factor (NGF) increase in skin after inflammation and induce CGRP in neurons in vivo and in vitro. This study was designed to understand how neurons integrate these two signals to regulate the neuropeptide important for inflammatory pain. In adult dorsal root ganglion neurons, NGF but not activin alone produced a dose-dependent increase in CGRP mRNA. When added together with NGF, activin synergistically increased CGRP mRNA, indicating that sensory neurons combine these signals. Studies were then designed to learn if that combination occurred at a common receptor or shared intracellular signals. Studies with Activin IB receptor or trkA inhibitors suggested that each ligand required its cognate receptor to stimulate the neuropeptide. Further, activin did not augment NGF-initiated intracellular MAPK signals but instead stimulated Smad phosphorylation, suggesting these ligands initiated parallel signals in the cytoplasm. Activin synergy required several NGF intracellular signals to be present. Because activin did not further stimulate, but did require NGF intracellular signals, it appears that activin and NGF converge not in receptor or cytoplasmic signals, but in transcriptional mechanisms to regulate CGRP in sensory neurons after inflammation. Keywords inflammation; neuropeptides; ERK; SmadHyperalgesia is a key sign of inflammation and is initiated by signals from inflamed tissues that act on sensory neurons to modify molecules involved in pain behaviors. The central mechanism of hyperalgesia involves the hyperexcitablility of dorsal horn neurons, which can be attenuated by blocking glutamate receptors Inturrisi, 2001, Yashpal et al., 2001), neurokinin receptors (Malmberg and Yaksh, 1992, Thompson et al., 1994) and CGRP receptors (Sun et al., 2004) in the spinal cord. Indeed, alpha-CGRP null mice do not develop hyperalgesia responses to inflammatory insults (Salmon et al., 2001, Zhang et al., 2001). The neuropeptide calcitonin gene related peptide (CGRP) is increased in sensory neurons after peripheral inflammation (Donaldson et al., 1992, Smith et al., 1992, Donnerer et al., 1993, Nahin and Byers, 1994, Seybold et al., 1995, Neumann et al., 1996, Malcangio et al., 1997, Mulder et al., 1997b, Durham and Russo, 1999, Calza et al., 2000, Bulling et al., 2001 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Salmon et al., 2001, Zha...

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Section: Discussionmentioning

confidence: 99%

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

Hall

2007

Neuroscience

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“…Distal axons were axotomized 5-7 d after plating by spraying cold, sterile water through a 0.22 gauge needle into the two side chambers. This process was repeated ϳ3-4 times, until all distal axons had been axotomized (Kimpinski et al, 1997;MacInnis et al, 2003). After axotomy, 2.5 g/ml C3-07 was added to the various compartments (i.e., cell body compartment only, distal axon compartments only, or all three compartments), and axonal growth into side chambers was measured 3 d after axotomy.…”

Section: Methodsmentioning

confidence: 99%

Application of Rho Antagonist to Neuronal Cell Bodies Promotes Neurite Growth in Compartmented Cultures and Regeneration of Retinal Ganglion Cell Axons in the Optic Nerve of Adult Rats

Bertrand¹,

Winton²,

et al. 2005

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Inactivation of Rho promotes neurite growth on inhibitory substrates and axon regeneration in vivo.Here, we compared axon growth when neuronal cell bodies or injured axons were treated with a cell-permeable Rho antagonist (C3-07) in vitro and in vivo. In neurons plated in compartmented cultures, application of C3-07 to either cell bodies or distal axons promoted axonal growth on myelinassociated glycoprotein substrates. In vivo, an injection of C3-07 into the eye promoted regeneration of retinal ganglion cell (RGC) axons in the optic nerve after microcrush lesion. Delayed application of C3-07 promoted RGC growth across the lesion scar. Application of C3-07 completely prevented RGC cell death for 1 week after axotomy. To investigate the mechanism by which Rho inactivation promotes RGC growth, we studied slow axonal transport. Reduction in slow transport of cytoskeletal proteins was observed after axotomy, but inactivation of Rho did not increase slow axonal transport rates. Together, our results indicate that application of a Rho antagonist at the cell body is neuroprotective and overcomes growth inhibition but does not fully prime RGCs for active growth.

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“…Fetal rat dorsal root ganglia (DRG) primary cultures were established essentially as described (24) from Harlan Sprague-Dawley day 17 rat embryos. All ganglia were dissected and dissociated first enzymatically with trypsin and then mechanically.…”

Section: Dissociated Neuronal Dorsal Root Ganglia Culturesmentioning

confidence: 99%

Genuine Monovalent Ligands of TrkA Nerve Growth Factor Receptors Reveal a Novel Pharmacological Mechanism of Action

Maliartchouk¹,

Debeir²,

Beglova³

et al. 2000

Journal of Biological Chemistry

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Developing small molecule agonistic ligands for tyrosine kinase receptors has been difficult, and it is generally thought that such ligands require bivalency. Moreover, multisubunit receptors are difficult to target, because each subunit contributes to ligand affinity, and each subunit may have distinct and sometimes opposing functions. Here, the nerve growth factor receptor subunits p75 and the tyrosine kinase TrkA were studied using artificial ligands that bind specifically to their extracellular domain. Bivalent TrkA ligands afford robust signals. However, genuine monomeric and monovalent TrkA ligands afford partial agonism, activate the tyrosine kinase activity, cause receptor internalization, and induce survival and differentiation in cell lines and primary neurons. Monomeric and monovalent TrkA ligands can synergize with ligands that bind the p75 subunit. However, the p75 ligands used in this study must be bivalent, and monovalent p75 ligands have no effect. These findings will be useful in designing and developing screens of small molecules selective for tyrosine kinase receptors and indicate that strategies for designing agonists of multisubunit receptors require consideration of the role of each subunit. Last, the strategy of using anti-receptor mAbs and small molecule hormone mimics as receptor ligands could be applied to the study of many other heteromeric cell surface receptors.

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Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures

Cited by 106 publications

References 46 publications

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons

Application of Rho Antagonist to Neuronal Cell Bodies Promotes Neurite Growth in Compartmented Cultures and Regeneration of Retinal Ganglion Cell Axons in the Optic Nerve of Adult Rats

Genuine Monovalent Ligands of TrkA Nerve Growth Factor Receptors Reveal a Novel Pharmacological Mechanism of Action

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