Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.
Neuroimmunomodulation

中文翻译：

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辛伐他汀通过抑制 A1 反应性星形胶质细胞预防帕金森病 MPTP 小鼠模型的神经变性

新出现的证据表明 A1 反应性星形胶质细胞在帕金森病 (PD) 的发病机制中起着至关重要的作用。因此，可抑制 A1 反应性星形胶质细胞形成的药物的开发可用于治疗 PD。辛伐他汀被吹捧为神经系统疾病（如 PD）的潜在神经保护剂，但具体的潜在机制尚不清楚。制备 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) PD 和原代星形胶质细胞/神经元小鼠模型，以研究辛伐他汀对 PD 的影响及其体外和体内的潜在机制。我们表明，辛伐他汀可防止 PD 的 MPTP 小鼠模型中多巴胺神经元的丢失和行为缺陷。我们还发现辛伐他汀在体内和体外抑制 A1 星形胶质细胞特异性标志物的表达。此外，辛伐他汀减轻了 A1 星形胶质细胞诱导的神经元死亡。我们的研究结果表明，辛伐他汀通过防止星形胶质细胞转化为 A1 神经毒性表型而具有神经保护作用。鉴于辛伐他汀的良好特性，应评估其治疗 PD 和以 A1 反应性星形胶质细胞为特征的相关神经系统疾病。
神经免疫调节