title: 7,8-dihydroxyflavone Ameliorates Motor Deficits Via Suppressing α-synuclein Expression and Oxidative Stress in the MPTP-induced Mouse Model of Parkinson's Disease.
abstract: 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.
  
  
  
  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 C57BL/6 mice.
  
  
  
  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.
  
  
  
  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 C57BL/6 mice.
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiao-Huan
authors.initials: XH
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Dai
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei-Tao
authors.initials: WT
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Han
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Dong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D047309:Flavones / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D020917:Receptor, trkA / Q000378:metabolism; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C485383:6,7-dihydroxyflavone; D000978:Antiparkinson Agents; D047309:Flavones; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D020917:Receptor, trkA
keywords: 7,8-dihydroxyflavone; Antioxidative activity; Dopaminergic neuron; MPTP; Parkinson disease; α-synuclein