In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin

Mol Cell Neurosci. 2000 Feb;15(2):199-214. doi: 10.1006/mcne.1999.0817.


The glial cell line-derived neurotrophic factor (GDNF)-family of neurotrophic factors consisted until recently of three members, GDNF, neurturin, and persephin. We describe here the cloning of a new GDNF-family member, neublastin (NBN), identical to artemin (ART), recently published (Baloh et al., 1998). Addition of NBN/ART to cultures of fetal mesencephalic dopamine (DA) neurons increased the number of surviving tyrosine hydroxylase (TH)-immunoreactive neurons by approximately 70%, similar to the maximal effect obtained with GDNF. To investigate the neuroprotective effects in vivo, lentiviral vectors carrying the cDNA for NBN/ART or GDNF were injected into the striatum and ventral midbrain. Three weeks after an intrastriatal 6-hydroxydopamine lesion only about 20% of the nigral DA neurons were left in the control group, while 80-90% of the DA neurons remained in the NBN/ART and GDNF treatment groups, and the striatal TH-immunoreactive innervation was partly spared. We conclude that NBN/ART, similarly to GDNF, is a potent neuroprotective factor for the nigrostriatal DA neurons in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular
  • Corpus Striatum / cytology*
  • Dopamine / physiology*
  • Gene Transfer Techniques
  • Genetic Vectors
  • Glial Cell Line-Derived Neurotrophic Factor
  • Humans
  • Lentivirus
  • Mice
  • Molecular Sequence Data
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / cytology*
  • Neurons / physiology*
  • Neuroprotective Agents
  • Rats
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substantia Nigra / cytology*
  • Tyrosine 3-Monooxygenase / analysis*


  • ARTN protein, human
  • Artn protein, mouse
  • Artn protein, rat
  • GDNF protein, human
  • Gdnf protein, mouse
  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Tyrosine 3-Monooxygenase
  • Dopamine