Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson's model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system
Kirik, Deniz LU ; Rosenblad, Carl ; Björklund, Anders LU
and Mandel, Ronald J
(2000)
In The Journal of Neuroscience
20(12).
p.4686-4700
- Abstract
- Previous studies have used recombinant adeno-associated viral (rAAV) vectors to deliver glial cell line-derived neurotrophic factor (GDNF) in the substantia nigra to protect the nigral dopamine (DA) neurons from 6-hydroxydopamine-induced damage. However, no regeneration or functional recovery was observed in these experiments. Here, we have used an rAAV-GDNF vector to express GDNF long-term (6 months) in either the nigral DA neurons themselves, in the striatal target cells, or in both of these structures. The results demonstrate that both nigral and striatal transduction provide significant protection of nigral DA neurons against the toxin-induced degeneration. However, only the rats receiving rAAV-GDNF in the striatum displayed behavioral... (More)
- Previous studies have used recombinant adeno-associated viral (rAAV) vectors to deliver glial cell line-derived neurotrophic factor (GDNF) in the substantia nigra to protect the nigral dopamine (DA) neurons from 6-hydroxydopamine-induced damage. However, no regeneration or functional recovery was observed in these experiments. Here, we have used an rAAV-GDNF vector to express GDNF long-term (6 months) in either the nigral DA neurons themselves, in the striatal target cells, or in both of these structures. The results demonstrate that both nigral and striatal transduction provide significant protection of nigral DA neurons against the toxin-induced degeneration. However, only the rats receiving rAAV-GDNF in the striatum displayed behavioral recovery, accompanied by significant reinnervation of the lesioned striatum, which developed gradually over the first 4-5 months after the lesion. GDNF transgene expression was maintained at high levels throughout this period. These results provide evidence that rAAV is a highly efficient vector system for long-term expression of therapeutic proteins in the nigrostriatal system. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1118296
- author
- Kirik, Deniz
LU
; Rosenblad, Carl
; Björklund, Anders
LU
and Mandel, Ronald J
- organization
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Neuroscience
- volume
- 20
- issue
- 12
- pages
- 4686 - 4700
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:10844038
- scopus:0034659835
- ISSN
- 1529-2401
- language
- English
- LU publication?
- yes
- id
- 7134132b-531d-4ac4-9fb9-d366a8629acb (old id 1118296)
- alternative location
- http://www.jneurosci.org/cgi/content/abstract/20/12/4686
- date added to LUP
- 2016-04-01 15:31:19
- date last changed
- 2023-10-30 13:32:14
@article{7134132b-531d-4ac4-9fb9-d366a8629acb,
abstract = {{Previous studies have used recombinant adeno-associated viral (rAAV) vectors to deliver glial cell line-derived neurotrophic factor (GDNF) in the substantia nigra to protect the nigral dopamine (DA) neurons from 6-hydroxydopamine-induced damage. However, no regeneration or functional recovery was observed in these experiments. Here, we have used an rAAV-GDNF vector to express GDNF long-term (6 months) in either the nigral DA neurons themselves, in the striatal target cells, or in both of these structures. The results demonstrate that both nigral and striatal transduction provide significant protection of nigral DA neurons against the toxin-induced degeneration. However, only the rats receiving rAAV-GDNF in the striatum displayed behavioral recovery, accompanied by significant reinnervation of the lesioned striatum, which developed gradually over the first 4-5 months after the lesion. GDNF transgene expression was maintained at high levels throughout this period. These results provide evidence that rAAV is a highly efficient vector system for long-term expression of therapeutic proteins in the nigrostriatal system.}},
author = {{Kirik, Deniz and Rosenblad, Carl and Björklund, Anders and Mandel, Ronald J}},
issn = {{1529-2401}},
language = {{eng}},
number = {{12}},
pages = {{4686--4700}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience}},
title = {{Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson's model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system}},
url = {{http://www.jneurosci.org/cgi/content/abstract/20/12/4686}},
volume = {{20}},
year = {{2000}},
}