Du Ren-Wei, Bu Wen-Guang
Department of Neurology, Chaoyang Hospital, Huainan, China,
Department of Neurology, Chaoyang Hospital, Huainan, China.
Neuroimmunomodulation. 2021;28(2):82-89. doi: 10.1159/000513678. Epub 2021 Mar 18.
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.
新出现的证据表明，A1反应性星形胶质细胞在帕金森病（PD）的发病机制中起关键作用。因此，开发能够抑制A1反应性星形胶质细胞形成的药物可用于治疗PD。辛伐他汀被誉为治疗诸如PD等神经疾病的潜在神经保护剂，但其具体潜在机制仍不清楚。制备了PD的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠模型以及原代星形胶质细胞/神经元，以研究辛伐他汀在体内外对PD的影响及其潜在机制。我们发现辛伐他汀可防止PD的MPTP小鼠模型中多巴胺能神经元的丢失和行为缺陷。我们还发现辛伐他汀在体内外均抑制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，应评估其在治疗以A1反应性星形胶质细胞为特征的PD及相关神经疾病中的作用。
