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Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor.
J Neurosci Res. 2000 May 15; 60(4):511-9.JN

Abstract

Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, that suggests potential uses of GDNF in the treatment of spinal cord injury and motor neuron diseases. We examined neuroprotective effect of human GDNF encoded by an adenovirus vector (AxCAhGDNF) on the death of lesioned adult rat spinal motoneurons. The seventh cervical segment (C7) ventral and dorsal roots and dorsal root ganglia of adult Fisher 344 rats were avulsed, and AxCAhGDNF, AxCALacZ (adenovirus encoding beta-galactosidase gene) or PBS was inoculated in C7 vertebral foramen. One week after the avulsion and treatment with AxCALacZ, the animals showed expression of beta-galactosidase activity in lesioned spinal motoneurons. Animals avulsed and treated with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal motoneurons and expression of virus-induced human GDNF mRNA transcripts in the lesioned spinal cord tissue. Nissl-stained cell counts revealed that the treatment with AxCAhGDNF significantly prevented the loss of lesioned ventral horn motoneurons 2 to 8 weeks after avulsion, as compared to AxCALacZ or PBS treatment. Furthermore, the AxCAhGDNF treatment ameliorated choline acetyltransferase immunoreactivity in the lesioned motoneurons after avulsion. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury and motor neuron diseases.

Authors+Show Affiliations

Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan. kazwtb@tmin.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10797554

Citation

Watabe, K, et al. "Rescue of Lesioned Adult Rat Spinal Motoneurons By Adenoviral Gene Transfer of Glial Cell Line-derived Neurotrophic Factor." Journal of Neuroscience Research, vol. 60, no. 4, 2000, pp. 511-9.
Watabe K, Ohashi T, Sakamoto T, et al. Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor. J Neurosci Res. 2000;60(4):511-9.
Watabe, K., Ohashi, T., Sakamoto, T., Kawazoe, Y., Takeshima, T., Oyanagi, K., Inoue, K., Eto, Y., & Kim, S. U. (2000). Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor. Journal of Neuroscience Research, 60(4), 511-9.
Watabe K, et al. Rescue of Lesioned Adult Rat Spinal Motoneurons By Adenoviral Gene Transfer of Glial Cell Line-derived Neurotrophic Factor. J Neurosci Res. 2000 May 15;60(4):511-9. PubMed PMID: 10797554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor. AU - Watabe,K, AU - Ohashi,T, AU - Sakamoto,T, AU - Kawazoe,Y, AU - Takeshima,T, AU - Oyanagi,K, AU - Inoue,K, AU - Eto,Y, AU - Kim,S U, PY - 2000/5/8/pubmed PY - 2000/7/6/medline PY - 2000/5/8/entrez SP - 511 EP - 9 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 60 IS - 4 N2 - Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, that suggests potential uses of GDNF in the treatment of spinal cord injury and motor neuron diseases. We examined neuroprotective effect of human GDNF encoded by an adenovirus vector (AxCAhGDNF) on the death of lesioned adult rat spinal motoneurons. The seventh cervical segment (C7) ventral and dorsal roots and dorsal root ganglia of adult Fisher 344 rats were avulsed, and AxCAhGDNF, AxCALacZ (adenovirus encoding beta-galactosidase gene) or PBS was inoculated in C7 vertebral foramen. One week after the avulsion and treatment with AxCALacZ, the animals showed expression of beta-galactosidase activity in lesioned spinal motoneurons. Animals avulsed and treated with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal motoneurons and expression of virus-induced human GDNF mRNA transcripts in the lesioned spinal cord tissue. Nissl-stained cell counts revealed that the treatment with AxCAhGDNF significantly prevented the loss of lesioned ventral horn motoneurons 2 to 8 weeks after avulsion, as compared to AxCALacZ or PBS treatment. Furthermore, the AxCAhGDNF treatment ameliorated choline acetyltransferase immunoreactivity in the lesioned motoneurons after avulsion. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury and motor neuron diseases. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/10797554/Rescue_of_lesioned_adult_rat_spinal_motoneurons_by_adenoviral_gene_transfer_of_glial_cell_line_derived_neurotrophic_factor_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0360-4012&date=2000&volume=60&issue=4&spage=511 DB - PRIME DP - Unbound Medicine ER -