期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 22, 期 7, 页码 617-624出版社
WILEY
DOI: 10.1111/cns.12555
关键词
7,8-dihydroxyflavone; Antioxidative activity; Dopaminergic neuron; MPTP; Parkinson disease; alpha-synuclein
资金
- 973 Program of the Ministry of Science and Technology of the People's Republic of China [2014CB548100]
- National Natural Science Foundation of China [81271221, 81571042, 81501143]
- Natural Science Foundation of Chongqing [cstc2015jcyjA00037]
Background: Parkinson disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and diminished dopamine content in the striatum, which is at least partly associated with alpha-synuclein protein overexpression in these neurons. Recent reports show that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects in animal model of PD. However, it is unclear whether the therapeutic effects of DHF are associated with the expression of alpha-synuclein. Aims: In this study, we investigated the protective effects of DHF on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)induced deficit of motor functions, the loss of dopaminergic neurons and the expression of alpha-synuclein as well as antioxidative activity in the C57BL/6 mice. Results: Mice were treated with MPTP (30 mg/kg, i.p.) once a day for 5 days to induce dopaminergic neuron death in the SN. DHF (5 mg/kg, i.p.) was administrated once a day from the first day of MPTP injection until 9 days after the last injection of MPTP. Behavioral tests showed that DHF succeeded in ameliorating the impaired motor functions in the MPTP-treated mice. The immunohistochemical assay showed that the amelioration of motor function was accompanied by a reduction in the loss of dopaminergic neurons in the SN and striatum. Western blot analyses showed that DHF prevented the inactivation of TrkB and suppressed alpha-synuclein overexpression in the SN and striatum following MPTP treatment. Antioxidative activity detection revealed that DHF prevented MPTP-induced reduction in glutathione and total superoxide dismutase activity in the SN and striatum. Conclusion: Taken together, these results indicate that DHF treatment may suppress the accumulation of alpha-synuclein and oxidative stress via activating TrkB and subsequently block the loss of dopaminergic neurons in the SN and striatum, thereby ameliorating MPTP-induced motor deficits in the C57BL/6 mice.
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