Effects and significance of α-synuclein on β-arrestin 2 expression in Parkinson' disease in a mouse model / 中华老年医学杂志

ABSTRACT

Objective:To investigate the effects and significance of α-synuclein(α-syn)on the expression level of β-arrestin 2 in Parkinson's disease(PD)in a mouse model.Methods:Twenty-eight C57BL/6J mice with similar motor skills were randomly divided into a model group and a control group, with 14 mice in each group.A PD model was established by injecting preformed fibrils of α-syn into the striatum of the brain, and behavioral changes were monitored after 4 weeks.The expression levels of α-syn, the dopamine receptor(DR), tyrosine hydroxylase(TH), inflammatory factors, β-arrestin 2 and the nuclear transcription factor-κB(NF-κB)signaling pathway-related proteins were determined by Western blotting.The interaction between α-syn and β-arrestin 2 was detected by fluorescence resonance energy transfer(FRET), and the regulation of α-syn on β-arrestin 2 transcriptional activation was detected by the dual luciferase report assay.Results:After 4 weeks of modeling, compared with the control group, the average movement speed of mice in the model group was significantly reduced( t=9.415, P<0.001), the movement track was sparse and concentrated around the open field, and the time needed to climb the pole was significantly prolonged( t=16.412, P<0.001). Compared with the control group, the relative expression of α-synin in astrocytes in the model group increased significantly, the relative expressions of D1DR and TH decreased significantly[(1.14±0.18) vs.(0.53±0.16), (0.67±0.13) vs.(1.15±0.11), (0.46±0.05) vs.(0.81±0.06)]( t=9.810, 10.917 and 17.356, all P<0.001), the relative expression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and NF-κB signaling pathway-related proteins increased significantly( t=3.583, 4.284, 5.396, 11.747, 16.375 and 18.294, all P<0.001), and the relative expression of β-arrestin 2 protein[(0.42±0.11) vs.(1.33±0.14)]in astrocytes decreased significantly( t=19.795, P<0.001). The FRET results suggested a possible direct interaction between α-syn and β-arrestin 2.The results of the dual luciferase report assay showed that the transcription activity of β-arrestin 2 was significantly increased after α-syn gene knockout. Conclusions:The α-syn may induce inflammation in astrocytes by activating the NF-κB signaling pathway and participate in the pathogenesis of PD by reducing dopamine biosynthesis and inhibiting its physiological function through negative regulation of β-arrestin 2.