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Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson’s disease

Neural Regeneration Research 2019年第8期14卷 1438-1444页

作者： Ai-Qin Wang Li-Na Kong Ming-Zhu Meng Xiu-He Zhao Si Chen Xiao-Tang Wang Qilu Hospital of Shandong University

Genome-wide studies have reported that Parkinson’s disease is associated with abnormal expression of various growth factors. In this study, male C57 BL/6 mice aged 10 weeks were used to establish Parkinson’s disease models using an intraperitoneal injection of 60 mg/kg 1-methyl-4-phenyl-1,2,3,6-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).

关键词： nerve regeneration Parkinson’s disease 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine fibroblast growth factor 20 a-type potassium current long-term potentiation Kv4.2 oxidative stress malondialdehyde motor performance neural regeneration

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