Pretreatment of glial cell-derived neurotrophic factor and geranylgeranylacetone ameliorates brain injury in Parkinson's disease by its anti-apoptotic and anti-oxidative property

: The aim of the present study was to determine the combined effects of glial cell-derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of PD and cellular models of H2 O2 and MPP+ -treated PC12 cells were established. Swimming, pole, and traction tests were used to detect behavioral impairment. Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis. MDA levels and activities of antioxidant enzymes were used to detect the oxidative damage. The PD model of mice received GDNF and GGA exhibited a significant recovery in their swim, pole, and traction scores. Moreover, the combined treatment significantly reduced the neuron apoptosis in the substantia nigra (SN) of PD mice or in H2 O2 or MPP+ -induced PC12 cells compared with the single drug group. In addition, significant reduction of MDA levels and improvement of activities of CAT, SOD, and GSH-px were observed after GDNF and GGA treatment in the PD model and H2 O2 or MPP+ -induced PC12 cells. The combination of GDNF and GGA ameliorated neural apoptosis and oxidative damage in PD.