Potential neuroprotective effect of low dose whole-body gamma-irradiation against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity in C57 mice

Low dose whole-body γ-irradiation is recently reported to confer neuroprotection against optic nerve crush and contusive spinal cord injury. Here, we extended the study and investigated whether the pretreatment of a single low dose whole-body γ-irradiation may have a preventive effect in MPTP-induced model of PD. One week after the last MPTP treatment, HPLC determination of striatal dopamine and immunostaining for tyrosine hydroxylase (TH), CD11b and GFAP to detect dopamine neurons and associated glial reaction in the substantia nigra pars compacta (SNpc) were performed. MPTP treatment reduced striatal DA levels significantly; nigral TH immunoreactivity was reduced to a lower extent; robust gliosis was also observed in SNpc. We found that 3.5 Gy irradiation but not 5.5 Gy restores the level of DA and its metabolites decreased by MPTP. However, there was no difference in the number of TH positive neurons between 3.5 Gy irradiated and saline treated mice after MPTP treatment. Irradiation also did not have obvious influence on microgliosis and astroglial reaction induced by MPTP treatment. In conclusion, the results presented here demonstrated that low dose whole-body γ-irradiation renders neuroprotection against MPTP-mediated damage of striatal dopaminergic nerve fibers, though it does not seem to influence the MPTP-induced reduction of SNpc dopaminergic neurons and associated glial responses.