Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea; College of Biosciences & Biotechnology, Chung-Nam National University, Daejeon, 34134, Republic of Korea.
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea; Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, 50463, Republic of Korea.
Neuropharmacology. 2020 Sep 15;175:108173. doi: 10.1016/j.neuropharm.2020.108173. Epub 2020 Jun 1.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes. We previously showed that co-treatment with metformin and 3,4-dihydroxyphenyl-l-alanine (l-DOPA) prevented the development of l-DOPA-induced dyskinesia in a 6-hydroxydopamine (6-OHDA)-lesioned animal model of PD. However, effects of metformin on PD- and aging-induced genes in reactive astrocytes remain unknown. In this study, we assessed the effect of metformin on motor function, neuroprotection, and reactive astrocytes in the 6-OHDA-induced PD animal model. In addition, the effects of metformin on the genes expressed by specific types of astrocytes were analyzed in PD model and aged mice. Here, we showed that metformin treatment effectively improves the motor symptoms in the 6-OHDA-induced PD mouse model, whereas metformin had no effect on tyrosine hydroxylase-positive neurons. The activation of AMPK and BDNF signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum. Metformin treatment caused astrocytes to alter reactive genes in a PD animal model. Moreover, aging-induced genes in reactive astrocytes were effectively regulated or suppressed by metformin treatment. Taken together, these results suggest that metformin should be evaluated for the treatment of Parkinson's disease and related neurologic disorders characterized by astrocyte activation.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质中多巴胺能神经元进行性丧失，导致运动症状。尽管近年来 PD 的管理取得了显著进展，但许多患者仍然严重残疾。二甲双胍是治疗 2 型糖尿病的主要药物。我们之前表明，二甲双胍和 3,4-二羟基苯丙氨酸（l-DOPA）联合治疗可预防 6-羟多巴胺（6-OHDA）诱导的 PD 动物模型中 l-DOPA 诱导的运动障碍的发展。然而，二甲双胍对 PD 和衰老诱导的反应性星形胶质细胞中的基因的影响尚不清楚。在这项研究中，我们评估了二甲双胍对 6-OHDA 诱导的 PD 动物模型中的运动功能、神经保护和反应性星形胶质细胞的影响。此外，还分析了二甲双胍对 PD 模型和老年小鼠中特定类型星形胶质细胞表达的基因的影响。在这里，我们表明二甲双胍治疗可有效改善 6-OHDA 诱导的 PD 小鼠模型中的运动症状，而二甲双胍对酪氨酸羟化酶阳性神经元没有影响。AMPK 和 BDNF 信号通路的激活是由 6-OHDA 损伤侧的纹状体中的二甲双胍治疗诱导的。二甲双胍治疗导致星形胶质细胞改变 PD 动物模型中的反应性基因。此外，二甲双胍治疗可有效调节或抑制衰老诱导的反应性星形胶质细胞中的基因。总之，这些结果表明，应该评估二甲双胍治疗以治疗以星形胶质细胞激活为特征的帕金森病和相关神经障碍。
