Neurotrophin-4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures

J Neurosci Res. 1994 Jan;37(1):144-54. doi: 10.1002/jnr.490370118.

Abstract

Parkinson's disease is a prevalent neurological disease characterized by profound and incapacitating movement disorders. A common pathology in Parkinson's patients is degeneration of substantia nigra dopaminergic neurons that innervate the striatum and a corresponding decrease in striatal dopamine content. We now report that NT-4/5 can prevent the death of rat embryonic substantia nigra dopaminergic neurons in low density, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT-4/5 and transcripts for NT-4/5 are present in their environment. In addition, we demonstrate that NT-4/5 protects embryonic dopaminergic neurons from the toxic effects of the neurotoxin MPP+. Thus, NT-4/5 could be a physiological survival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for Parkinson's disease.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity
  • Animals
  • Cell Survival
  • Cells, Cultured
  • Corpus Striatum / chemistry
  • Corpus Striatum / cytology
  • Corpus Striatum / embryology
  • Dopamine / metabolism*
  • Nerve Growth Factors / pharmacology
  • Nerve Growth Factors / physiology*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology
  • Neurons / cytology*
  • Neurons / drug effects
  • Parkinson Disease / metabolism
  • Polymerase Chain Reaction
  • Rats
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Growth Factor / biosynthesis
  • Receptors, Growth Factor / genetics
  • Substantia Nigra / cytology*
  • Substantia Nigra / embryology
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / biosynthesis
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Growth Factor
  • neurotrophin 5
  • Tyrosine 3-Monooxygenase
  • neurotrophin 4
  • 1-Methyl-4-phenylpyridinium
  • Dopamine