In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin.
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.
Rosenblad
C
C
Wallenberg Neuroscience Center, Lund University, Solvegatan 17, Lund, S-223 62, Sweden. carl.rosenblad@mphy.lu.se
Grønborg
M
M
Hansen
C
C
Blom
N
N
Meyer
M
M
Johansen
J
J
Dagø
L
L
Kirik
D
D
Patel
U A
UA
Lundberg
C
C
Trono
D
D
Björklund
A
A
Johansen
T E
TE
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D018696:Neuroprotective Agents; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013378:Substantia Nigra / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*
C490886:ARTN protein, human; C116599:Artn protein, mouse; C490887:Artn protein, rat; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine