Open Access7,8‐dihydroxyflavone Ameliorates Motor Deficits Via Suppressing α ‐synuclein Expression and Oxidative Stress in the MPTP ‐induced Mouse Model of Parkinson's Disease
Author(s) -
Li XiaoHuan,
Dai ChunFang,
Chen Long,
Zhou WeiTao,
Han HuiLi,
Dong ZhiFang
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12555
Subject(s) - mptp , dopaminergic , substantia nigra , striatum , parkinson's disease , oxidative stress , dopamine , endocrinology , chemistry , medicine , pharmacology , neurotoxin , western blot , biochemistry , disease , gene
Summary 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 α ‐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 α ‐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 α ‐synuclein as well as antioxidative activity in the C57 BL /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 α ‐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 α ‐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 C57 BL /6 mice.