The role of DAT regulated by GDNF of midbrain in Parkinson disease and its mechanism

Objective To explore the role of dopamine transporter (DAT) regulated by glial cell line-derived neurotrophic factor (GDNF) of midbrain in Parkinson disease (PD) and related mechanism. Methods Adeno-associated virus were used to interfere with the expression of GDNF and DAT in the midbrain of PD model mice respectively. The motor function of mice were evaluated by behavior tests. The expression of GDNF, DAT and tyrosine hydroxylase (TH) were detected by Western blot. The distribution of TH⁺ neurons in the substantia nigra was observed by immunofluorescence. Dopamine (DA) levels in the substantia nigra and striatum were detected by ELISA. Results Down-regulation of GDNF in the midbrain of PD model mice resulted in a reduction in both duration on the rod and total distance of activity of mice, a decrease in both TH distribution and DAT expression in the substantia nigra, as well as a decrease in DA level in both the substantia nigra and striatum. Down-regulation of DAT in the midbrain of PD model mice resulted in a reduction in both duration on the rod and total distance of activity of mice, a decrease in TH distribution in the substantia nigra, a decrease in both DAT and TH expression in the substantia nigra, as well as a decrease in DA level in both the substantia nigra and striatum. Conclusions GDNF can regulate DA transmission in the nigrostriatal pathway through DAT.Decreased GDNF in the midbrain may contribute to DA dysfunction through down-regulating DAT, thereby promoting the loss of DA neurons and the development of motor symptoms of PD.