Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion
(2007) In The Journal of Neuroscience 27(3). p.459-471- Abstract
- Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2... (More)
- Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1143437
- author
- Timmer, Marco ; Cesnulevicius, Konstantin ; Winkler, Christian LU ; Kolb, Julia ; Lipokatic-Takacs, Esther ; Jungnickel, Julia and Grothe, Claudia
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Neuroscience
- volume
- 27
- issue
- 3
- pages
- 459 - 471
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:17234579
- scopus:33846436077
- pmid:17234579
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.4493-06.2007
- language
- English
- LU publication?
- no
- id
- de9d6647-53bf-49e6-ad14-1a71a9fa5b2a (old id 1143437)
- date added to LUP
- 2016-04-01 16:43:38
- date last changed
- 2023-09-05 00:09:06
@article{de9d6647-53bf-49e6-ad14-1a71a9fa5b2a,
abstract = {{Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.}},
author = {{Timmer, Marco and Cesnulevicius, Konstantin and Winkler, Christian and Kolb, Julia and Lipokatic-Takacs, Esther and Jungnickel, Julia and Grothe, Claudia}},
issn = {{1529-2401}},
language = {{eng}},
number = {{3}},
pages = {{459--471}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience}},
title = {{Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.4493-06.2007}},
doi = {{10.1523/JNEUROSCI.4493-06.2007}},
volume = {{27}},
year = {{2007}},
}