Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease

Abstract

The clinical use of fetal neural grafts as an intracerebral source of dopamine for patients with Parkinson's disease has met with limited success. Since basic fibroblast growth factor (bFGF) enhances the survival and growth of dopaminergic neurons in vitro, we explored whether cells genetically modified to produce bFGF would improve the functional efficacy of dopaminergic neurons implanted into rats with experimental Parkinson's disease. Results show that bFGF-producing cells grafted together with fetal dopamine neurons have potent growth-promoting effects on the implanted neurons in vivo. Moreover, rats implanted with such co-grafts display the most pronounced behavioural improvements post-grafting. These findings not only provide insight into the function of bFGF in situ, but also suggest an approach for enhancing the survival and function of dopamine neurons grafted into the damaged brain.

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

“…Otto and Unsicker, 1993). bFGF also increases dopaminergic graft survival and function in a rat model of Parkinson's disease (Takayama et al, 1995). Fibroblasts that have been genetically engineered to produce bFGF and implanted into the striatum attenuate damage caused by intrastriatal injection of 6-OHDA (Shults et al, 2000).…”

Driving GDNF expression: The green and the red traffic lights

“…FGF-2 exerts a potent neuroprotective action on nigral dopaminergic neurons in the MPTP mouse model of PD Unsicker, 1990, 1993;Chadi et al, 1993). FGF-2 also increases dopaminergic graft survival and function in a rat model of PD (Takayama et al, 1995). Moreover, fibroblasts genetically engineered to produce FGF-2 and implanted into the striatum attenuate the damage caused by intrastriatal injection of 6-OHDA (Shults et al, 2000).…”

Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

“…bFGF has been demonstrated to be a potent trophic agent for embryonic, neonate and adult dopamine cells in vitro and in vivo (19,52,53), while aFGF requires heparin for its effects on fetal midbrain neurons (19). Cells genetically modified to produce bFGF have potent growth-promoting effects and function on fetal dopamine neurons implanted into rats with experimental parkinsonism (54). Although bFGF immunoreactivity is not modified in dopaminergic neurons of the substantia nigra during normal aging in humans, it is reduced in this cell group of patients with Parkinson's disease (55), which suggests its role in neurodegenerative disorders.…”