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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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

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

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