Axonal outgrowth and neuronal apoptosis in cultured adult mouse dorsal root ganglion preparations: effects of neurotrophins, of inhibition of neurotrophin actions and of prior axotomy

Edström, Anders; Ekström, Per; Tonge, David

doi:10.1016/0306-4522(96)00324-7

Cited by 61 publications

(47 citation statements)

References 36 publications

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“…In keeping with our observations, others have reported that NT-3 did not reduce axotomy-induced neuronal apoptosis in DRG explant cultures, whilst glial cell linederived neurotrophic factor (GDNF) did (Edström et al, 1996;Leclere et al, 1997). Furthermore, we did not observe a significantly higher number of neurons in the ipsilateral ganglia from animals treated with the higher dose of NT-3, compared with the lower dose.…”

Section: Nt-3 and Neuron Losssupporting

confidence: 92%

Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Kuo¹,

Simpson²,

Schänzer³

et al. 2005

J of Comparative Neurology

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Previous work has shown that administration of the neurotrophin NT-3 intrathecally or to the proximal stump can prevent axotomy-induced sensory neuron loss and that NT-3 can stimulate sensory neuron differentiation in vitro. We have examined the effect of axotomy and systemic NT-3 administration on neuronal loss, apoptosis (defined by morphology and activated caspase-3 immunoreactivity), and nestin expression (a protein expressed by neuronal precursor cells) in dorsal root ganglia (DRG) following axotomy of the adult rat sciatic nerve. Systemic administration of 1.25 or 5 mg of NT-3 over 1 month had no effect on the incidence of apoptotic neurons but prevented the overall loss of neurons seen at 4 weeks in vehicle-treated animals. Nestin-immunoreactive neurons began to appear 2 weeks after sciatic transection in untreated animals and steadily increased in incidence over the next 6 weeks. NT-3 administration increased the number of nestin-immunoreactive neurons at 1 month by two- to threefold. Nestin-IR neurons had a mean diameter of 20.78 +/- 2.5 microm and expressed the neuronal markers neurofilament 200, betaIII-tubulin, protein gene product 9.5, growth associated protein 43, trkA, and calcitonin gene-related peptide. Our results suggest that the presence of nestin in DRG neurons after nerve injury is due to recent differentiation and that exogenous NT-3 may prevent neuron loss by stimulating this process, rather than preventing neuron death.

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Section: Nt-3 and Neuron Losssupporting

confidence: 92%

Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Kuo¹,

Simpson²,

Schänzer³

et al. 2005

J of Comparative Neurology

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“…It is well established that dissociated DRG neurons of adult rats and mice can extend neurites in the presence of laminin in the absence of added neurotrophic factors and that this outgrowth is greatly enhanced by previous axotomy in vivo (Hu-Tsai et al, 1994;Edström et al, 1996;Smith and Pate Skene, 1997;Lankford et al, 1998;Liu and Snider, 2001;Ekström et al, 2003). In the present study, we found that neurons labeled by RT97 showed profuse spontaneous neurite outgrowth on laminin, but that neurite outgrowth from the IB4-labeled neurons was markedly inferior.…”

Section: Discussionsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

“…NGF, NT-3, and GDNF also promote axonal regeneration of adult neurons (Mohiuddin et al, 1995;Edström et al, 1996;Naveilhan et al, 1997;Leclere et al, 1998;Gavazzi et al, 1999;Ramer et al, 2000;Fine et al, 2002). BDNF does not stimulate growth of DRG axons in adult rodents (Malgrange et al, 1994;Edström et al, 1996;Kimpinski et al, 1997;Gavazzi et al, 1999), but BDNF and NT-4 both stimulate axonal growth from nodose ganglia (Wiklund and Ekström, 2000). After peripheral nerve (PN) lesions, synthesis of NGF, BDNF, NT-4, and GDNF increases (Meyer et al, 1992;Funakoshi et al, 1993;Trupp et al, 1995;Naveilhan et al, 1997;Bar et al, 1998;Hoke et al, 2000Hoke et al, , 2002Dethleffsen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…After peripheral nerve (PN) lesions, synthesis of NGF, BDNF, NT-4, and GDNF increases (Meyer et al, 1992;Funakoshi et al, 1993;Trupp et al, 1995;Naveilhan et al, 1997;Bar et al, 1998;Hoke et al, 2000Hoke et al, , 2002Dethleffsen et al, 2002). Because NGF and GDNF stimulate axonal growth from DRG neurons in vitro and in vivo (Edström et al, 1996;Naveilhan et al, 1997;Leclere et al, 1998;Gavazzi et al, 1999;Ramer et al, 2000;Fine et al, 2002), their upregulation in lesioned peripheral nerves might be expected to promote axonal regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Impaired Axonal Regeneration by Isolectin B4-Binding Dorsal Root Ganglion NeuronsIn Vitro

Leclere¹,

Norman²,

Groutsi³

et al. 2007

J. Neurosci.

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The subpopulation of dorsal root ganglion (DRG) neurons recognized by Griffonia simplicifolia isolectin B4 (IB4) differ from other neurons by expressing receptors for glial cell line-derived neurotrophic factor (GDNF) rather than neurotrophins. Additionally, IB4-labeled neurons do not express the laminin receptor, ␣7-integrin (Gardiner et al., 2005), necessary for optimal axonal regeneration in the peripheral nervous system. In cultures of dissociated DRG neurons of adult mice on laminin, robust spontaneous neurite outgrowth from IB4-negative neurons occurs and is strongly enhanced by previous axotomy. In contrast, IB4-labeled neurons show little neurite outgrowth and do not express GAP 43, even after axotomy or culture with GDNF. Moreover, growth of their axons through collagen gels is impaired compared with other DRG neurons. To determine whether the sparse neurite outgrowth of IB4-labeled neurons is attributable to lack of integrin expression, DRG cultures were infected with a herpes simplex 1 vector encoding ␣7-integrin, but its forced expression failed to promote neurite outgrowth in either IB4-labeled or other DRG neurons or in cultured adult retinal ganglion cells. Forced coexpression of both ␣7-integrin and GAP 43 also failed to promote neurite outgrowth in IB4-labeled neurons. In addition, cultured sciatic nerve segments were found to release much lower levels of GDNF, demonstrated by ELISA, than nerve growth factor. These findings together with their impaired intrinsic axonal regeneration capacity may contribute to the known vulnerability of the IB4-labeled population of DRG neurons to peripheral nerve injury.

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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

1997

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We used compartmented cultures to study the regulation of adult sensory neurite growth by neurotrophins. We examined the effects of the neurotrophins nerve growth factor (NGF), neurotrophin‐3 (NT3), and BDNF on distal neurite elongation from adult rat dorsal root ganglion (DRG) neurons. Neurons were plated in the center compartments of three‐chambered dishes in the absence of neurotrophin, and neurite extension into the distal (side) compartments containing NGF, BDNF, or NT3 was quantitated. Initial proximal neurite growth did not require any of the neurotrophins, while subsequent elongation into distal compartments required NGF. After neurites had extended into NGF‐containing distal compartments, removal of NGF by treatment with anti‐NGF resulted in the cessation of growth with minimal neurite retraction. In contrast to the effects of NGF, no distal neurite elongation was observed into compartments with BDNF or NT3. To examine possible additive influences, neurite extension into compartments containing BDNF plus NGF or NT3 plus NGF was quantitated. There was no increased neurite extension into NGF plus NT3 compartments, while the combination of BDNF plus NGF resulted in an inhibition of neurite extension compared with NGF alone. We then investigated whether the regrowth of neurites that had originally grown into NGF subsequent to in vitro axotomy still required NGF. The results demonstrated that unlike adult sensory nerve regeneration in vivo, the in vitro regrowth did require NGF, and neither BDNF nor NT3 was able to substitute for NGF. Since the initial growth from neurons after dissociation (which is also a regenerative response) did not require NGF, it would appear that neuritic growth and regrowth of adult DRG neurons in vitro includes both NGF‐independent and NGF‐dependent components. The compartmented culture system provides a unique model to further study aspects of this differential regulation of neurite growth. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 395–410, 1997

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Axonal outgrowth and neuronal apoptosis in cultured adult mouse dorsal root ganglion preparations: effects of neurotrophins, of inhibition of neurotrophin actions and of prior axotomy

Cited by 61 publications

References 36 publications

Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Impaired Axonal Regeneration by Isolectin B4-Binding Dorsal Root Ganglion NeuronsIn Vitro

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

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