FGF-2 deficiency does not alter vulnerability of the dopaminergic nigrostriatal system towards MPTP intoxication in mice

Autor:	Irina Kiprianova, Klaus Unsicker, Andreas Schober, J. Jarosik, O. von Bohlen und Halbach, Sabrina Zechel
Rok vydání:	2006
Předmět:	medicine.medical_specialty Tyrosine hydroxylase General Neuroscience MPTP Dopaminergic Substantia nigra Striatum Biology Midbrain chemistry.chemical_compound Endocrinology nervous system chemistry Neurotrophic factors Dopamine Internal medicine medicine Neuroscience medicine.drug
Zdroj:	European Journal of Neuroscience. 23:1671-1675
ISSN:	0953-816X
DOI:	10.1111/j.1460-9568.2006.04700.x
Popis:	Fibroblast growth factor 2 (FGF-2) was the first growth factor discovered that exerted prominent protective and regenerative effects in an animal model of Parkinson's disease, the MPTP-lesioned dopaminergic nigrostriatal system. To address the putative physiological relevance of endogenous FGF-2 for midbrain dopaminergic neurons, we have analysed densities of tyrosine hydroxylase (TH)positive cells in the substantia nigra (SN) and TH-positive fibers in the striatum and amygdala of adult FGF-2-deficient mice. We found that densities of TH-immunoreactive (ir) cells in the SN as well as densities of TH-ir fibers in the striatum and amygdala were unaltered as compared with wild-type littermates. There is evidence to suggest that growth factor deficits do not become apparent unless a system is challenged in a lesioning paradigm. We therefore tested the ability of the nigrostriatal system with respect to its ability to cope with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxication. Treatment with 20 mg/kg MPTP on three consecutive days reduced dopamine levels in the striatum by about 80%. Densities of TH-positive neurons in the SN were reduced by 71%. However, both parameters did not significantly differ between FGF-2 (-/-) mice and wild-type littermates. Our results therefore suggest that FGF-2, despite its prominent pharmacological potency as a neurotrophic factor for the dopaminergic nigrostriatal system, is not crucial for maintaining its structural integrity and ability to cope with MPTP intoxication.
Databáze:	OpenAIRE
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