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Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector.

Georgievska, Biljana LU ; Kirik, Deniz LU ; Rosenblad, Carl; Lundberg, Cecilia LU and Björklund, Anders LU (2002) In NeuroReport 13(1). p.75-82
Abstract
We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model.The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for > 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side).... (More)
We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model.The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for > 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF. (Less)
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keywords
Lentivirus : genetics, Luminescent Proteins : pharmacokinetics, Motor Activity : drug effects, Nerve Tissue Proteins : genetics, Nerve Tissue Proteins : pharmacokinetics, Nerve Tissue Proteins : therapeutic use, Neurons : drug effects, Neurons : metabolism, Neuroprotective Agents : therapeutic use, Oxidopamine : pharmacology, Parkinson Disease : pathology, Parkinson Disease : physiopathology, Parkinson Disease : therapy, Rats, Sprague-Dawley, Substantia Nigra : drug effects, Substantia Nigra : pathology, Support, Non-U.S. Gov't, Tyrosine 3-Monooxygenase : metabolism, Indicators and Reagents : pharmacokinetics, Genetic Vectors, Gene Transfer Techniques, Female, Dopamine : metabolism, Corpus Striatum : pathology, Corpus Striatum : drug effects, Animal
in
NeuroReport
volume
13
issue
1
pages
75 - 82
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:11924898
  • wos:000173449000020
  • scopus:0037148074
ISSN
1473-558X
language
English
LU publication?
yes
id
effc8cf9-8704-4dc8-a679-b98f33b468bb (old id 107304)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11924898&dopt=Abstract
date added to LUP
2007-07-12 13:22:59
date last changed
2017-11-19 03:29:51
@article{effc8cf9-8704-4dc8-a679-b98f33b468bb,
  abstract     = {We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model.The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for > 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF.},
  author       = {Georgievska, Biljana and Kirik, Deniz and Rosenblad, Carl and Lundberg, Cecilia and Björklund, Anders},
  issn         = {1473-558X},
  keyword      = {Lentivirus : genetics,Luminescent Proteins : pharmacokinetics,Motor Activity : drug effects,Nerve Tissue Proteins : genetics,Nerve Tissue Proteins : pharmacokinetics,Nerve Tissue Proteins : therapeutic use,Neurons : drug effects,Neurons : metabolism,Neuroprotective Agents : therapeutic use,Oxidopamine : pharmacology,Parkinson Disease : pathology,Parkinson Disease : physiopathology,Parkinson Disease : therapy,Rats,Sprague-Dawley,Substantia Nigra : drug effects,Substantia Nigra : pathology,Support,Non-U.S. Gov't,Tyrosine 3-Monooxygenase : metabolism,Indicators and Reagents : pharmacokinetics,Genetic Vectors,Gene Transfer Techniques,Female,Dopamine : metabolism,Corpus Striatum : pathology,Corpus Striatum : drug effects,Animal},
  language     = {eng},
  number       = {1},
  pages        = {75--82},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {NeuroReport},
  title        = {Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector.},
  volume       = {13},
  year         = {2002},
}