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

Author

  • Carl Rosenblad
  • M Gronborg
  • C Hansen
  • N Blom
  • M Meyer
  • J Johansen
  • L Dago
  • Deniz Kirik
  • U A Patel
  • Cecilia Lundberg
  • D Trono
  • A Bjorklund
  • T E Johansen

Summary, in English

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.

Publishing year

2000

Language

English

Pages

199-214

Publication/Series

Molecular and Cellular Neuroscience

Volume

15

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Status

Published

Research group

  • Brain Repair and Imaging in Neural Systems (BRAINS)
  • CNS Gene Therapy

ISBN/ISSN/Other

  • ISSN: 1044-7431