Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease

Isobel J Sleeman, Eugene L Boshoff, Susan Duty

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Abstract

Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro, through activation of fibroblast growth factor receptor 1 (FGFR1). This study set out to examine whether FGF-20 also displayed protective efficacy in the unilateral, 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH-positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH staining was also demonstrated in the substantia nigra pars compacta (SNpc) of naïve adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 μg/day) for 6 days post-lesion gave significant protection (∼40%) against the loss of TH-positive cells in the SNpc and the loss of striatal TH immunoreactivity. This protection of the nigrostriatal tract was accompanied by a significant preservation of gross locomotion and fine motor movements and reversal of apomorphine-induced contraversive rotations, although forelimb akinesia, assessed using cylinder test reaching, was not improved. These results support a role for FGF-20 in preserving dopamine neuron integrity and some aspects of motor function in a rodent model of Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in this disease.

Original languageEnglish
Pages (from-to)1268-77
Number of pages10
JournalNeuropharmacology
Volume63
Issue number7
Early online date10 Aug 2012
DOIs
Publication statusPublished - Dec 2012

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Fibroblast Growth Factors
Oxidopamine
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Parkinson Disease
Receptor, Fibroblast Growth Factor, Type 1
Neurons
Corpus Striatum
Forelimb
Apomorphine
Poisons
Substantia Nigra
Locomotion
Rodentia
Staining and Labeling
Brain

Keywords

  • Animals
  • Corpus Striatum/drug effects
  • Dopaminergic Neurons/drug effects
  • Fibroblast Growth Factors/pharmacology
  • Male
  • Motor Activity/drug effects
  • Nerve Degeneration/chemically induced
  • Oxidopamine
  • Parkinson Disease, Secondary/chemically induced
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Fibroblast Growth Factor, Type 1/metabolism
  • Substantia Nigra/drug effects
  • Tyrosine 3-Monooxygenase/metabolism

Cite this

@article{1953def4a62b4e44b59e1d9af58316e9,
title = "Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease",
abstract = "Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro, through activation of fibroblast growth factor receptor 1 (FGFR1). This study set out to examine whether FGF-20 also displayed protective efficacy in the unilateral, 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH-positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH staining was also demonstrated in the substantia nigra pars compacta (SNpc) of na{\"i}ve adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 μg/day) for 6 days post-lesion gave significant protection (∼40{\%}) against the loss of TH-positive cells in the SNpc and the loss of striatal TH immunoreactivity. This protection of the nigrostriatal tract was accompanied by a significant preservation of gross locomotion and fine motor movements and reversal of apomorphine-induced contraversive rotations, although forelimb akinesia, assessed using cylinder test reaching, was not improved. These results support a role for FGF-20 in preserving dopamine neuron integrity and some aspects of motor function in a rodent model of Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in this disease.",
keywords = "Animals, Corpus Striatum/drug effects, Dopaminergic Neurons/drug effects, Fibroblast Growth Factors/pharmacology, Male, Motor Activity/drug effects, Nerve Degeneration/chemically induced, Oxidopamine, Parkinson Disease, Secondary/chemically induced, Rats, Rats, Sprague-Dawley, Receptor, Fibroblast Growth Factor, Type 1/metabolism, Substantia Nigra/drug effects, Tyrosine 3-Monooxygenase/metabolism",
author = "Sleeman, {Isobel J} and Boshoff, {Eugene L} and Susan Duty",
note = "Copyright {\circledC} 2012 Elsevier Ltd. All rights reserved. Acknowledgements The authors would like to thank Carl Hobbs for expert technical advice with the immunohistochemistry. These studies were supported by a UK Medical Research Council PhD Studentship and a Capacity Building Award in Integrative Mammalian Biology funded by the BBSRC, BPS, HEFCE, KTN, MRC and SFC. The funding bodies had no role in either conducting these studies or in compiling the manuscript for publication.",
year = "2012",
month = "12",
doi = "10.1016/j.neuropharm.2012.07.029",
language = "English",
volume = "63",
pages = "1268--77",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",
number = "7",

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TY - JOUR

T1 - Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease

AU - Sleeman, Isobel J

AU - Boshoff, Eugene L

AU - Duty, Susan

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved. Acknowledgements The authors would like to thank Carl Hobbs for expert technical advice with the immunohistochemistry. These studies were supported by a UK Medical Research Council PhD Studentship and a Capacity Building Award in Integrative Mammalian Biology funded by the BBSRC, BPS, HEFCE, KTN, MRC and SFC. The funding bodies had no role in either conducting these studies or in compiling the manuscript for publication.

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N2 - Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro, through activation of fibroblast growth factor receptor 1 (FGFR1). This study set out to examine whether FGF-20 also displayed protective efficacy in the unilateral, 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH-positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH staining was also demonstrated in the substantia nigra pars compacta (SNpc) of naïve adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 μg/day) for 6 days post-lesion gave significant protection (∼40%) against the loss of TH-positive cells in the SNpc and the loss of striatal TH immunoreactivity. This protection of the nigrostriatal tract was accompanied by a significant preservation of gross locomotion and fine motor movements and reversal of apomorphine-induced contraversive rotations, although forelimb akinesia, assessed using cylinder test reaching, was not improved. These results support a role for FGF-20 in preserving dopamine neuron integrity and some aspects of motor function in a rodent model of Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in this disease.

AB - Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro, through activation of fibroblast growth factor receptor 1 (FGFR1). This study set out to examine whether FGF-20 also displayed protective efficacy in the unilateral, 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH-positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH staining was also demonstrated in the substantia nigra pars compacta (SNpc) of naïve adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 μg/day) for 6 days post-lesion gave significant protection (∼40%) against the loss of TH-positive cells in the SNpc and the loss of striatal TH immunoreactivity. This protection of the nigrostriatal tract was accompanied by a significant preservation of gross locomotion and fine motor movements and reversal of apomorphine-induced contraversive rotations, although forelimb akinesia, assessed using cylinder test reaching, was not improved. These results support a role for FGF-20 in preserving dopamine neuron integrity and some aspects of motor function in a rodent model of Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in this disease.

KW - Animals

KW - Corpus Striatum/drug effects

KW - Dopaminergic Neurons/drug effects

KW - Fibroblast Growth Factors/pharmacology

KW - Male

KW - Motor Activity/drug effects

KW - Nerve Degeneration/chemically induced

KW - Oxidopamine

KW - Parkinson Disease, Secondary/chemically induced

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Fibroblast Growth Factor, Type 1/metabolism

KW - Substantia Nigra/drug effects

KW - Tyrosine 3-Monooxygenase/metabolism

U2 - 10.1016/j.neuropharm.2012.07.029

DO - 10.1016/j.neuropharm.2012.07.029

M3 - Article

C2 - 22971544

VL - 63

SP - 1268

EP - 1277

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 7

ER -