Kopaeva Marina Yu, Cherepov Anton B, Nesterenko Mikhail V, Zarayskaya Irina Yu
National Research Center «Kurchatov Institute», 1 Akademika Kurchatova sq., 123182 Moscow, Russia.
«Lactobio» LLC, 29 Prospekt Vernadskogo, 119331 Moscow, Russia.
Biology (Basel). 2021 Jan 1;10(1):24. doi: 10.3390/biology10010024.
We studied the effect of human lactoferrin (hLf) on degenerative changes in the nigrostriatal system and associated behavioral deficits in the animal model of Parkinson disease. Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral disturbances were assessed in the open field and rotarod tests and by the stride length analysis. Structural deficits were assessed by the counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and optical density (OD) of TH-immunolabeled fibers in the striatum. Acute MPTP treatment induced long-term behavioral deficit and degenerative changes in the nigrostriatal system. Pretreatment with hLf prevented body weight loss and promoted recovery of motor functions and exploratory behavior. Importantly, OD of TH-positive fibers in the striatum of mice treated with hLf almost returned to normal, and the number of TH-positive cells in the substantia nigra significantly increased on day 28. These results indicate that hLf produces a neuroprotective effect and probably stimulates neuroregeneration under conditions of MPTP toxicity in our model. A relationship between behavioral deficits and nigrostriatal system disturbances at delayed terms after MPTP administration was found.
我们研究了人乳铁蛋白(hLf)对帕金森病动物模型中黑质纹状体系统退行性变化及相关行为缺陷的影响。通过向5月龄C57Bl/6小鼠单次注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP;40 mg/kg)诱导黑质纹状体多巴胺能损伤。在旷场试验、转棒试验以及通过步长分析评估行为障碍。通过黑质中酪氨酸羟化酶(TH)免疫反应性神经元计数和纹状体中TH免疫标记纤维的光密度(OD)评估结构缺陷。急性MPTP处理诱导了黑质纹状体系统的长期行为缺陷和退行性变化。hLf预处理可防止体重减轻,并促进运动功能和探索行为的恢复。重要的是,hLf处理的小鼠纹状体中TH阳性纤维的OD几乎恢复正常,并且在第28天黑质中TH阳性细胞的数量显著增加。这些结果表明,在我们的模型中,hLf在MPTP毒性条件下产生神经保护作用,并可能刺激神经再生。发现了MPTP给药后延迟期行为缺陷与黑质纹状体系统紊乱之间的关系。