Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation

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

doi:10.1006/exnr.2001.7753

Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation

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

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

This study examined the role of glial cell line-derived neurotrophic factor (GDNF) in synaptic plasticity at the developing neuromuscular junction. Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age indicated that GDNF mRNA and protein levels were elevated threefold in the lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in the number of cholinesterase-positive end plates without changes in end-plate area. Multiple end plates on a single muscle fiber were also observed, in addition to multiple axonal processes terminating on individual end plates. No change in the number of spinal motoneurons, overall LGM size, or muscle type composition was observed. Finally, overexpression of GDNF in muscle caused hypertrophy of neuronal somata in dorsal root ganglia without affecting their number. These findings demonstrate that overexpression of a single neurotrophic factor in skeletal muscle induces multiple end-plate formation and maintains hyperinnervation well beyond the normal developmental period. We suggest that GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role in the regulation of synaptic plasticity in the developing and adult neuromuscular junction.

Original language	English
Pages (from-to)	342-350
Number of pages	9
Journal	Experimental Neurology
Volume	171
Issue number	2
DOIs	https://doi.org/10.1006/exnr.2001.7753
State	Published - 2001

Bibliographical note

Funding Information:
This work was supported by Grant NS-30248 from the National Institutes of Health and The University of Kentucky Research Foundation to Joe E. Springer and by Grant NS-31826 from the National Institutes of Health to Brian M. Davis. The authors thank S. Kennedy and M. Green for their excellent technical assistance and Dr. K. Albers for input and assistance in establishing the transgenic lines. We also thank Dr. D. Wright, Dr. M. Werle, Dr. J. Brueckner, and P. Crumrine for helpful comments.

Funding

This work was supported by Grant NS-30248 from the National Institutes of Health and The University of Kentucky Research Foundation to Joe E. Springer and by Grant NS-31826 from the National Institutes of Health to Brian M. Davis. The authors thank S. Kennedy and M. Green for their excellent technical assistance and Dr. K. Albers for input and assistance in establishing the transgenic lines. We also thank Dr. D. Wright, Dr. M. Werle, Dr. J. Brueckner, and P. Crumrine for helpful comments.

Funders	Funder number
University of Kentucky and São Paulo Research Foundation
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke	R01NS031826

Keywords

Glial cell line-derived neurotrophic factor
Hyperinnervation
Motoneurons
Multiple end plates
Neuromuscular junctions
Target-derived
Transgenic

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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10.1006/exnr.2001.7753

Cite this

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title = "Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation",

abstract = "This study examined the role of glial cell line-derived neurotrophic factor (GDNF) in synaptic plasticity at the developing neuromuscular junction. Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age indicated that GDNF mRNA and protein levels were elevated threefold in the lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in the number of cholinesterase-positive end plates without changes in end-plate area. Multiple end plates on a single muscle fiber were also observed, in addition to multiple axonal processes terminating on individual end plates. No change in the number of spinal motoneurons, overall LGM size, or muscle type composition was observed. Finally, overexpression of GDNF in muscle caused hypertrophy of neuronal somata in dorsal root ganglia without affecting their number. These findings demonstrate that overexpression of a single neurotrophic factor in skeletal muscle induces multiple end-plate formation and maintains hyperinnervation well beyond the normal developmental period. We suggest that GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role in the regulation of synaptic plasticity in the developing and adult neuromuscular junction.",

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author = "Melissa Zwick and Lihong Teng and Xiaojun Mu and Springer, {Joe E.} and Davis, {Brian M.}",

note = "Funding Information: This work was supported by Grant NS-30248 from the National Institutes of Health and The University of Kentucky Research Foundation to Joe E. Springer and by Grant NS-31826 from the National Institutes of Health to Brian M. Davis. The authors thank S. Kennedy and M. Green for their excellent technical assistance and Dr. K. Albers for input and assistance in establishing the transgenic lines. We also thank Dr. D. Wright, Dr. M. Werle, Dr. J. Brueckner, and P. Crumrine for helpful comments.",

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AU - Zwick, Melissa

AU - Teng, Lihong

AU - Mu, Xiaojun

AU - Springer, Joe E.

AU - Davis, Brian M.

N1 - Funding Information: This work was supported by Grant NS-30248 from the National Institutes of Health and The University of Kentucky Research Foundation to Joe E. Springer and by Grant NS-31826 from the National Institutes of Health to Brian M. Davis. The authors thank S. Kennedy and M. Green for their excellent technical assistance and Dr. K. Albers for input and assistance in establishing the transgenic lines. We also thank Dr. D. Wright, Dr. M. Werle, Dr. J. Brueckner, and P. Crumrine for helpful comments.

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N2 - This study examined the role of glial cell line-derived neurotrophic factor (GDNF) in synaptic plasticity at the developing neuromuscular junction. Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age indicated that GDNF mRNA and protein levels were elevated threefold in the lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in the number of cholinesterase-positive end plates without changes in end-plate area. Multiple end plates on a single muscle fiber were also observed, in addition to multiple axonal processes terminating on individual end plates. No change in the number of spinal motoneurons, overall LGM size, or muscle type composition was observed. Finally, overexpression of GDNF in muscle caused hypertrophy of neuronal somata in dorsal root ganglia without affecting their number. These findings demonstrate that overexpression of a single neurotrophic factor in skeletal muscle induces multiple end-plate formation and maintains hyperinnervation well beyond the normal developmental period. We suggest that GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role in the regulation of synaptic plasticity in the developing and adult neuromuscular junction.

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Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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