Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson's disease
摘要Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors.In this study,male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-meth yl-4-phenyl-l,2,3,6-tetrahydropyridine.28 days later,10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly.The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp.Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay.Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay.The motor coordination of mice was evaluated using the rotarod test.The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra,increased long-term potentiation amplitude in the hippocampus,and downregulated Kv4.2 expression.A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice.These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,and its mechanism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression.All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University,China in 2017 (approval No.KYLL-2017-0012).
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