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PMID: 12358802 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Developmental alteration of nerve injury induced glial cell line-derived neurotrophic factor (GDNF) receptor expression is crucial for the determination of injured motoneuron fate.

Journal of neurochemistry ·Vol. 82 ·No. 4 ·2002-08-00 ·Pages 961-75

Honma M, Namikawa K, Mansur K, Iwata T, Mori N, Iizuka H, Kiyama H

Abstract

Axotomy-induced neuronal death occurs in neonatal motoneurons, but not in adult rat. Here we demonstrated that during the course of postnatal development, nerve injury induced down-regulation of the glial cell line-derived neurotrophic factor (GDNF) receptor GFRalpha1 in axotomized hypoglossal motoneurons of rat are gradually converted to the adult up-regulation pattern of response. The compensatory expression of GFRalpha1 specifically in the injured motoneurons of neonates by adenovirus succeeded in rescuing the injured neurons without an application of growth factors. To the contrary, the nuclear antisense RNA for GFRalpha1 expression accelerates the axotomy-induced neuronal death in pups. These findings suggest that the receptor expression response after nerve injury is critical for the determination of injured motoneuron fate.

MeSH Terms
Age Factors Animals Animals, Newborn Axotomy Brain-Derived Neurotrophic Factor/pharmacology Cell Death/drug effects Cell Line Down-Regulation Drosophila Proteins Gene Expression Regulation, Developmental/drug effects Genetic Vectors/administration & dosage,genetics Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Humans Hypoglossal Nerve/growth & development,metabolism Hypoglossal Nerve Injuries Immunohistochemistry In Situ Hybridization Membrane Glycoproteins Mononeuropathies/metabolism Motor Neurons/cytology,drug effects,metabolism Nerve Growth Factors Nerve Tissue Proteins/pharmacology Proto-Oncogene Proteins/genetics,metabolism,pharmacology Proto-Oncogene Proteins c-ret RNA, Antisense/pharmacology RNA, Messenger/antagonists & inhibitors,metabolism Rats Rats, Wistar Receptor Protein-Tyrosine Kinases/genetics,metabolism,pharmacology Receptors, Cell Surface/genetics,metabolism Receptors, Nerve Growth Factor Up-Regulation
Chemicals
Brain-Derived Neurotrophic Factor Drosophila Proteins GDNF protein, human GFRA1 protein, human Gdnf protein, rat Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Membrane Glycoproteins Nerve Growth Factors Nerve Tissue Proteins Proto-Oncogene Proteins RNA, Antisense RNA, Messenger Receptors, Cell Surface Receptors, Nerve Growth Factor Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Honma Masaru
Department of Anatomy, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
Namikawa Kazuhiko
Mansur Khalil
Iwata Tatsuya
Mori Nozomu
Iizuka Hajime
Kiyama Hiroshi
Article Info
Journal
Journal of neurochemistry
Abbr.
J Neurochem
ISSN
0022-3042
Published
2002-08-00
Pages
961-75
Language
English
Region
England
NLM ID
2985190R
Subset
IM
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