Evidence That the Loss of Homeostatic Signals Induces Regeneration-Associated Alterations in Neuronal Gene Expression

Wu, Wendong; Mathew, T.C.; Miller, Freda D.

doi:10.1006/dbio.1993.1203

Cited by 51 publications

(37 citation statements)

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“…Application of vinblastine led to an increase in GAP-43 mRNA expression in hypoglossal motor neurons and to upregulated ␣-calcitonin gene-related peptide mRNA in rat motoneurons (Katoh et al, 1992;Kobayashi et al, 1994). Furthermore, ␣-tubulin and p75 NGFR mRNA levels are increased in facial motor neurons after coldblock treatment that leads to selective block of fast axonal transport (Wu et al, 1993). Taken together, these studies point towards a significant role of retrograde signaling pathways propagated along microtubules, in the repression of GAP genes.…”

Section: An Intact Cytoskeleton Is Necessary For Gap-43 and ␣-Tubulinmentioning

confidence: 77%

Target contact regulates GAP-43 and ?-tubulin mRNA levels in regenerating retinal ganglion cells

et al. 1998

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Axotomy of vertebrate neurons leads to the transient upregulation of GAP-43 and alpha-tubulin. In adult zebrafish retina, mRNA levels of both genes were increased in retinal ganglion cells after optic nerve lesion following a similar time course. At 5 days after crush, the mRNA level of GAP-43 was increased nearly 20 times, whereas a 6-fold increase was observed for alpha-tubulin. Subsequently, upon target reinnervation, mRNA levels of both genes were downregulated and were 2-fold higher than normal at 25 days after crush. Stretching the optic nerve that results in diffuse axonal lesions led to the expression of both genes in identical subsets of retinal ganglion cells. When regeneration was prevented by removing a piece of the optic nerve, mRNA levels remained elevated. Disruption of axonal transport by colchicine and vinblastine led to the induction of both genes in normal retina. Blocking electrical activity with tetrodotoxin had no effect. This indicates that retrogradely transported signals induced by target contact regulate GAP-43 and alpha-tubulin transcription. Furthermore, the joint regulation of GAP-43 and alpha-tubulin mRNA levels after different kinds of lesion suggests that a common pathway underlies the regulation of neuronal GAP-43 and alpha-tubulin gene expression. In contrast, distinct mechanisms may control the extent and maintenance of increased mRNA levels of these genes.

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Section: An Intact Cytoskeleton Is Necessary For Gap-43 and ␣-Tubulinmentioning

confidence: 77%

Target contact regulates GAP-43 and ?-tubulin mRNA levels in regenerating retinal ganglion cells

et al. 1998

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“…Abundant TrkC immunoreactivity has been shown in several cortical layers, including layer 5 Pitts and Miller, 2000), and p75 immunoreactivity is inducible by several stimuli including lesions in many cortical areas (Botchkina et al, 1997;Roux et al, 1999;Shi and Mocchetti, 2000) and after axotomy in spinal motoneurons (Wu et al, 1993). To examine whether the respective proteins localize to unlesioned and /or axotomized corticospinal neurons, we performed immunohistochemistry for the neurotrophin receptors on sections from animals that received unilateral axotomy of FB-labeled C SNs.…”

Section: Methodsmentioning

confidence: 99%

Endogenous Brain-Derived Neurotrophic Factor and Neurotrophin-3 Antagonistically Regulate Survival of Axotomized Corticospinal NeuronsIn Vivo

et al. 2001

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Neuronal growth factors regulate the survival of neurons by their survival and death-promoting activity on distinct populations of neurons. The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) promote neuronal survival via tyrosine kinase (Trk) receptors, whereas NGF and BDNF can also induce apoptosis in developing neurons through p75 NTR receptors in the absence of their respective Trk receptors. Using mutant mice and inactivation of neurotrophins and their receptors with antibodies in rats, we show that endogenous NT-3 induces death of adult BDNF-dependent, axotomized corticospinal neurons (CSNs). When NT-3 is neutralized, the neurons survive even without BDNF, suggesting complete antagonism. Whereas virtually all unlesioned and axotomized CSNs express both trkB and trkC mRNA, p75 is barely detectable in unlesioned CSNs but strongly upregulated in axotomized CSNs by day 3 after lesion, the time point when cell death occurs. Blocking either cortical TrkC or p75 NTR receptors alone prevents death, indicating that the opposing actions of NT-3 and BDNF require their respective Trk receptors, but induction of death depends on p75 NTR cosignaling. The results show that neuronal survival can be regulated antagonistically by neurotrophins and that neurotrophins can induce neuronal death in the adult mammalian CNS. We further present evidence that signaling of tyrosine kinase receptors of the trk family can be crucially involved in the promotion of neuronal death in vivo.

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“…In adult peripheral neurons, growth-associated genes (e.g., GAP-43) can be up-regulated in response to target loss (Verzé et al, 1996) or blockade of axonal transport (Woolf et al, 1990;Wu et al, 1993). In addition, the cellular/molecular changes induced by axotomy are typically reversed when the severed axons rejoin their terminal fields, but they are maintained for long periods if regeneration is prevented (Bisby, 1988;Woolf et al, 1990;Schreyer and Skene, 1991;Fernandes and Tetzlaff, 2001).…”

Section: Target-derived Factorsmentioning

confidence: 99%

Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System

Rossi

2006

Model Organisms in Spinal Cord Regeneration

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Evidence That the Loss of Homeostatic Signals Induces Regeneration-Associated Alterations in Neuronal Gene Expression

Cited by 51 publications

References 0 publications

Target contact regulates GAP-43 and ?-tubulin mRNA levels in regenerating retinal ganglion cells

Target contact regulates GAP-43 and ?-tubulin mRNA levels in regenerating retinal ganglion cells

Endogenous Brain-Derived Neurotrophic Factor and Neurotrophin-3 Antagonistically Regulate Survival of Axotomized Corticospinal NeuronsIn Vivo

Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System

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