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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 orcid and Björklund, Anders LU orcid (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
2016-04-01 11:53:56
date last changed
2022-01-26 19:53:51
@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}},
  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}},
  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.}},
  url          = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11924898&dopt=Abstract}},
  volume       = {{13}},
  year         = {{2002}},
}