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