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

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

PY - 2012/12

Y1 - 2012/12

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 naive adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 mu g/day) for 6 days post-lesion gave significant protection (similar to 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 naive adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 mu g/day) for 6 days post-lesion gave significant protection (similar to 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.

U2 - 10.1016/j.neuropharm.2012.07.029

DO - 10.1016/j.neuropharm.2012.07.029

M3 - Article

SN - 0028-3908

VL - 63

SP - 1268

EP - 1277

JO - Neuropharmacology

JF - Neuropharmacology

IS - 7

ER -