GDNF reduces oxidative stress in a 6-hydroxydopamine model of Parkinson's disease

Many current theories of Parkinson's disease (PD) suggest that oxidative stress is involved in the neurodegenerative process. Potential neuroprotective agents could protect neurons through inherent antioxidant properties or through the upregulation of the brain's antioxidant defenses. Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect and restore dopamine neurons in experimental models of PD and to improve motor function in human patients. This study was designed to investigate GDNF's effect on oxidative stress in a model of PD. GDNF or vehicle was injected into the right striatum of male Fischer-344 rats. Three days later 6-OHDA or saline was injected into the same striatum. The striatum and substantia nigra from both sides of the brain were removed 24h after 6-OHDA or saline injection and analyzed for the oxidative stress markers protein carbonyls and 4-hydroxynonenal. Both markers were significantly reduced in GDNF+6-OHDA treated animals compared to vehicle+6-OHDA treated animals. In addition, in animals allowed to recover for 3.5-4 weeks after the 6-OHDA administration, the GDNF led to significant protection against loss of striatal and nigral tissue levels of dopamine. These results suggest that the protective effects of GDNF against 6-OHDA involve a reduction in oxidative stress.