Overexpression of GDNF Induces and Maintains Hyperinnervation of Muscle Fibers and Multiple End-Plate Formation

Zwick, Melissa; Teng, Lihong; Mu, Xiaojun; Springer, Joe E.; Davis, Brian M.

doi:10.1006/exnr.2001.7753

Cited by 62 publications

(55 citation statements)

References 37 publications

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“…2001) and lentiviral expression of GDNF in vitro rescues adult mouse facial motoneurons from injury-induced cell death (Hottinger et al, 2000). A recent study has also demonstrated that GDNF serves an essential role in regulating synaptic plasticity at the neuromuscular junction (Zwick et al, 2001). In the present study, GDNF had a potent effect on motoneuron survival consistent with previous findings.…”

Section: Discussionsupporting

confidence: 89%

GDNF and BDNF Alter the Expression of Neuronal NOS, c-Jun, and p75 and Prevent Motoneuron Death following Spinal Root Avulsion in Adult Rats

Yick

et al. 2003

Journal of Neurotrauma

104

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In the present study, we examined the effects of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin growth factor (IGF-1) on adult motoneuron survival following spinal root avulsion. The expression of neuronal nitric oxide synthase (nNOS), c-Jun, and the low-affinity neurotrophin receptor (P75) following treatment with these neurotrophic factors was also examined. In control animals, approximately 80% of spinal motoneurons were nNOS positive at 3 weeks following the lesion, whereas in GDNF or BDNF treated animals no nNOS positive motoneurons were found at the same time point. Following injury and treatment with GDNF and BDNF increased numbers of motoneurons were c-Jun and P75 positive. By 6 weeks following the lesion, only approximately 28% of motoneurons persisted in control animals whereas about 90% of motoneurons survived injury following treatment with either GDNF or BDNF. In contrast, CNTF and IGF-1 were ineffective in either inhibiting nNOS expression or preventing motoneuron death. Our results provide in vivo evidence that the survival of injured adult mammalian motoneurons can be promoted by specific neurotrophic factors, and that this effect is associated with inhibition of nNOS expression and up-regulation of c-Jun and P75 expression.

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Section: Discussionsupporting

confidence: 89%

GDNF and BDNF Alter the Expression of Neuronal NOS, c-Jun, and p75 and Prevent Motoneuron Death following Spinal Root Avulsion in Adult Rats

Yick

et al. 2003

Journal of Neurotrauma

104

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“…42 While NGF activity was shown to be critical for axonal spouting, 43 studies with overexpressed GDNF is skeletal muscles have shown a significant elevation of cholinesterase-positive end plates in muscle fibers. 44 A recent study has also indicated strong synergistic effects of VEGF and GDNF in the prolonged survival of muscle motor end plates and motor neurons in a rat amyotrophic lateral sclerosis model of disease. 45 These findings suggest that the observed increase in the expression of both factors upon VEGF delivery plays a critical role in the maintenance and the de novo formation of motor axon units in ischemic skeletal muscles.…”

Section: Discussionmentioning

confidence: 97%

Sustained Delivery of VEGF Maintains Innervation and Promotes Reperfusion in Ischemic Skeletal Muscles Via NGF/GDNF Signaling

et al. 2014

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Tissue reinnervation following trauma, disease, or transplantation often presents a significant challenge. Here, we show that the delivery of vascular endothelial growth factor (VEGF) from alginate hydrogels ameliorates loss of skeletal muscle innervation after ischemic injury by promoting both maintenance and regrowth of damaged axons in mice. Nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) mediated VEGF-induced axonal regeneration, and the expression of both is induced by VEGF presentation. Using both in vitro and in vivo modeling approaches, we demonstrate that the activity of NGF and GDNF regulates VEGF-driven angiogenesis, controlling endothelial cell sprouting and blood vessel maturation. Altogether, these studies produce evidence of new mechanisms of VEGF action, further broaden the understanding of the roles of NGF and GDNF in angiogenesis and axonal regeneration, and suggest approaches to improve axonal and ischemic tissue repair therapies.

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“…GDNF is also important for maintenance of the neuromuscular junction itself. Administration of GDNF to the muscle in the rat results in motor unit enlargement and synaptic remodeling (KellerPeck et al, 2001), and over-expression of muscle GDNF induces multiple end-plate formation and maintains hyper-innervation (Zwick et al, 2001), suggesting that GDNF modifies the pre-and postsynaptic apparatus at the neuromuscular junction. Elevated GDNF in denervated muscle may contribute to maintaining the postsynaptic apparatus of the muscle and may enhance nerve regeneration by increasing the contact of motor nerve with its end organ.…”

Section: Altered Expression Of Gdnf In the Muscle By Sensory Protectionmentioning

confidence: 97%

NGF, BDNF, NT-3, and GDNF mRNA Expression in Rat Skeletal Muscle following Denervation and Sensory Protection

Zhao

Veltri

et al. 2004

Journal of Neurotrauma

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Poor muscle and nerve functional recovery after nerve damage is a serious clinical problem, particularly if there is prolonged delay before nerve-muscle contact is reestablished. Our previous studies showed that sensory nerve cross-anastomosis (sensory protection) provides support to the denervated muscle. In the present study, we analyzed neurotrophic factor mRNA expression by RT-PCR in denervated rat gastrocnemius muscle receiving sensory protection with the saphenous nerve, compared to normal innervated muscle, to denervated muscle, and to denervated muscle repaired immediately with the peroneal (motor) nerve, after periods of 3 days to 3 months. No significant differences in mRNA levels of beta-actin, nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3 were found between the sensory protection treatment and the denervated or the motor repair groups. However, sensory protection resulted in levels of muscle glial cell line-derived neurotrophic factor mRNA expression that were lower than in denervated muscle and higher than in muscle given immediate motor repair. These results demonstrate that glial cell line-derived neurotrophic factor mRNA is elevated following denervation but is partially down-regulated by sensory protection. Our study suggests that sensory protection provides a modified trophic environment by modulating neurotrophic factor synthesis in muscle.

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Overexpression of GDNF Induces and Maintains Hyperinnervation of Muscle Fibers and Multiple End-Plate Formation

Cited by 62 publications

References 37 publications

GDNF and BDNF Alter the Expression of Neuronal NOS, c-Jun, and p75 and Prevent Motoneuron Death following Spinal Root Avulsion in Adult Rats

GDNF and BDNF Alter the Expression of Neuronal NOS, c-Jun, and p75 and Prevent Motoneuron Death following Spinal Root Avulsion in Adult Rats

Sustained Delivery of VEGF Maintains Innervation and Promotes Reperfusion in Ischemic Skeletal Muscles Via NGF/GDNF Signaling

NGF, BDNF, NT-3, and GDNF mRNA Expression in Rat Skeletal Muscle following Denervation and Sensory Protection

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