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

J Neurochem. 2002 Aug;82(4):961-75. doi: 10.1046/j.1471-4159.2002.01043.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

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
  • Genetic Vectors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Humans
  • Hypoglossal Nerve / growth & development
  • Hypoglossal Nerve / metabolism*
  • Hypoglossal Nerve Injuries*
  • Immunohistochemistry
  • In Situ Hybridization
  • Membrane Glycoproteins*
  • Mononeuropathies / metabolism*
  • Motor Neurons / cytology
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / pharmacology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / pharmacology
  • Proto-Oncogene Proteins c-ret
  • RNA, Antisense / pharmacology
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases / pharmacology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Nerve Growth Factor*
  • Up-Regulation

Substances

  • 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