Effects of ketamine on expression of α-synuclein in Parkinson's disease mice

AIM:To observe the effect of treatment with ketamine (Ket) on the expression of α-synuclein (α-Syn) in a mouse model of Parkinson's disease (PD) induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS:Healthy male mice (n=48) were randomly divided into 3 groups:NaCl group (control group), MPTP group (model group) and MPTP+Ket group (treatment group). Rotarod experiment and gait analysis system were used to evaluate the behavioral differences among the animals in 3 groups. Immunohistochemical staining was used to observe the change of tyrosine hydroxylase (TH) expression in neurons of substantia nigra. Immunofluorescence staining and Western blot were used to detect the protein expression of α-Syn in substantia nigra and striatum region. RESULTS:According to the results of rotarod experiment and gait analysis system, the number of laps and the step length in MPTP group were reduced significantly as compared with NaCl group (P<0.05), while those in MPTP+Ket group showed significant increases as compared with MPTP group (P<0.05). The results of immunohistochemical staining and immunofluorescence staining indicated that the number of dopaminergic neurons in substantia nigra was decreased, and the fluorescence intensity for α-Syn in substantia nigra and striatum was increased in MPTP group as compared with NaCl group (P<0.05). The number of dopaminergic neurons in substantia nigra was increased, and the fluorescence intensity in substantia nigra and striatum was decreased in MPTP+Ket group as compared with MPTP group (P<0.05). The results of Western blot also indicated that the protein expression of α-Syn in substantia nigra and striatum region augmented significantly in MPTP group as compared with NaCl group (P<0.05). Compared with MPTP group, the protein expression of α-Syn in MPTP+Ket group was significantly decreased (P<0.05). CONCLUSION:Ketamine has a convinced inhibitory effect on the abnormal expression of α-Syn in the substantia nigra and striatum region of the PD mice.