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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Therapeutic activation of autophagy by combined treatment with rapamycin and trehalose in a mouse MPTP-induced model of Parkinson's disease
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Therapeutic activation of autophagy by combined treatment with rapamycin and trehalose in a mouse MPTP-induced model of Parkinson's disease

机译：用雷帕霉素诱导的小鼠MPTP诱导的帕金森病模型中雷帕霉素和海藻糖治疗治疗疗法

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The neuroprotective effect of autophagy activation by rapamycin and trehalose was studied in a mouse model of Parkinson's disease (PD) induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both rapamycin (10 mg/kg/day, 7 days) and trehalose (2% in drinking water, 7 days) increased the expression of LC3-II (a marker of autophagy activation) in the frontal cortex and striatum of normal C57B1/6J mice, with signs of an additive effect. Autophagy stimulation in the striatum was confirmed by a lysosomal osmotic test. In the model of MPTP-induced PD, the two drugs were applied starting from the 2nd day after subchronic daily MPTP administration (20 mg/kg/day, 4 days). A marked increase in LC3-II expression in the striatum was detected under the action of trehalose and in the S. nigra after combined treatment with rapamycin and trehalose. The drugs had a positive effect for recovery of dopaminergic neurons and neuroprotection after MPTP-induced PD-like injury. The therapeutic effect was proven by active restoration of tyrosine hydroxylase (TH) content in the striatum and S. nigra and by improved cognition measured by the passive avoidance learning task. The results revealed the additive effect of the combined treatment with rapamycin and trehalose on dopaminergic deficits (according to the levels of TH expression in the nigrostriatal system) but not on the behavioral performance in the mouse PD model. Thus, the autophagy activation through different pathways by the combination of rapamycin and trehalose reverses both neuronal dopaminergic and behavioral deficits in vivo and seems to be a promising therapy for PD-like pathology.
机译：通过毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病（Pd）小鼠模型研究了雷帕霉素和海藻糖的自噬菌素和海藻糖的神经保护作用。雷帕霉素（10mg / kg /天，7天）和海藻糖（饮用水中的2％，7天）增加了正常C57b1 / 6j的额叶和纹状体中LC3-II（自噬激活标志物）的表达小鼠，具有添加剂效果的迹象。通过溶酶体渗透性试验证实了纹状体中的自噬刺激。在MPTP诱导的PD模型中，从次级每日MPTP给药后的第2天（20mg / kg /天，4天）开始，从第2天开始施用两种药物。在与雷帕霉素和海藻糖组合后，在海藻糖和S. nigra的作用下检测纹状体中LC3-II表达的显着增加。药物对MPTP诱导的Pd样损伤后的多巴胺能神经元和神经保护作用的恢复积极效果。通过在纹状体和S. nigra中的酪氨酸羟化酶（Th）含量的活跃恢复和通过被动避免学习任务测量的改善认知来证明治疗效果。结果表明，雷帕霉素和海藻糖对多巴胺能缺陷的组合治疗的添加效应（根据核符号系统中的表达水平），但不是对小鼠PD模型中的行为性能。因此，通过雷帕霉素和海藻糖组合的不同途径的自噬激活反转了体内神经元多巴胺能和行为缺陷，并且似乎是PD样病理的有希望的治疗。

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