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

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 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 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 C57BL/6 mice.

• Authors: Xiao-Huan Li, Chun-Fang Dai, Long Chen, Wei-Tao Zhou, Hui-Li Han, Zhi-Fang Dong
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 22 Issue 7 Pg. 617-24 (07 2016) ISSN: 1755-5949 [Electronic] England
• PMID: 27079181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• 6,7-dihydroxyflavone
• Antiparkinson Agents
• Flavones
• alpha-Synuclein
• Tyrosine 3-Monooxygenase
• Receptor, trkA

Topics

• Analysis of Variance
• Animals
• Antiparkinson Agents (therapeutic use)
• Cell Death (drug effects)
• Disease Models, Animal
• Flavones (therapeutic use)
• Gene Expression Regulation (drug effects)
• MPTP Poisoning (drug therapy, metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Movement (drug effects)
• Oxidative Stress (drug effects)
• Psychomotor Performance (drug effects)
• Receptor, trkA (metabolism)
• Rotarod Performance Test
• Tyrosine 3-Monooxygenase (metabolism)
• alpha-Synuclein (metabolism)