Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor.
(2004) In European Journal of Neuroscience 20(11). p.3121-3130- Abstract
- The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80–90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in... (More)
- The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80–90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in control (green fluorescent protein-overexpressing) animals. However, in animals that were allowed to survive for 6 months, the numbers of surviving TH-positive cells in the grafts were equal in both groups, suggesting that the cells initially protected at 4 weeks failed to survive despite the continued presence of GDNF. Although cell survival was similar in both grafted groups, the TH-positive fiber innervation density was lower in the GDNF-treated grafted animals (30% of normal) compared with animals with control grafts (55% of normal). The vesicular monoamine transporter-2-positive fiber density in the striatum, by contrast, was equal in both groups, suggesting that long-term GDNF overexpression induced a selective down-regulation of TH in the grafted dopamine neurons. Behavioral analysis in the long-term grafted animals showed that the control grafted animals improved their performance in spontaneous motor behaviors to approximately 50% of normal, whereas the GDNF treatment did not provide any additional recovery. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/132162
- author
- Georgievska, Biljana LU ; Carlsson, Thomas LU ; Lacar, Benjamin ; Winkler, Christian LU and Kirik, Deniz LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Neuroscience
- volume
- 20
- issue
- 11
- pages
- 3121 - 3130
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:15579166
- wos:000225487800030
- scopus:10844229392
- pmid:15579166
- ISSN
- 1460-9568
- DOI
- 10.1111/j.1460-9568.2004.03770.x
- language
- English
- LU publication?
- yes
- id
- cf7ed533-ec75-414b-a0c2-a875ff2717f4 (old id 132162)
- date added to LUP
- 2016-04-01 11:43:21
- date last changed
- 2022-04-13 00:19:11
@article{cf7ed533-ec75-414b-a0c2-a875ff2717f4,
abstract = {{The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80–90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in control (green fluorescent protein-overexpressing) animals. However, in animals that were allowed to survive for 6 months, the numbers of surviving TH-positive cells in the grafts were equal in both groups, suggesting that the cells initially protected at 4 weeks failed to survive despite the continued presence of GDNF. Although cell survival was similar in both grafted groups, the TH-positive fiber innervation density was lower in the GDNF-treated grafted animals (30% of normal) compared with animals with control grafts (55% of normal). The vesicular monoamine transporter-2-positive fiber density in the striatum, by contrast, was equal in both groups, suggesting that long-term GDNF overexpression induced a selective down-regulation of TH in the grafted dopamine neurons. Behavioral analysis in the long-term grafted animals showed that the control grafted animals improved their performance in spontaneous motor behaviors to approximately 50% of normal, whereas the GDNF treatment did not provide any additional recovery.}},
author = {{Georgievska, Biljana and Carlsson, Thomas and Lacar, Benjamin and Winkler, Christian and Kirik, Deniz}},
issn = {{1460-9568}},
language = {{eng}},
number = {{11}},
pages = {{3121--3130}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Neuroscience}},
title = {{Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor.}},
url = {{https://lup.lub.lu.se/search/files/2611555/624283.pdf}},
doi = {{10.1111/j.1460-9568.2004.03770.x}},
volume = {{20}},
year = {{2004}},
}