He Weiliang, Tian Xiaochao, Yuan Bilin, Chu Bao, Gao Fan, Wang Hebo
a Department of Neurology , Hebei General Hospital , Shijiazhuang , Hebei , PR China.
b Department of Cardiology , Second Hospital of Hebei Medical University , Shijiazhuang , Hebei , PR China.
Neurol Res. 2019 Jul;41(7):658-664. doi: 10.1080/01616412.2019.1610226. Epub 2019 Apr 25.
: Neurite outgrowth of neurons is essential for forming functional neural circuits. It is believed that neuronal neurite outgrowth is an important mechanism of brain plasticity. Rosuvastatin (RSV) is a relatively new statin and may have neuroprotective properties. However, whether RSV exerts an effect on neurite extension and its potential mechanism in cortical neurons remains poorly documented. : Immunofluorescence method was used to examine the effect of RSV on neurite outgrowth in primary cortical neuron by measuring neurite length and confirmed the promotion effect. Then, the potential mechanisms involving the Notch1 pathway were investigated. Effects of RSV on the expression of Notch 1 and Hes1were determined using qRT-PCR. In addition, brain-derived neurotrophic factor (BDNF) expression was also assessed using qRT-PCR, and ELISA. : RSV promoted neurite outgrowth of cortical neurons, and this effect could be partially prevented by the Notch 1 pathway inhibitor, DAPT. Subsequently, we found that Jagged 1 and Notch 1 were colocalized. In addition, we observed that the levels of both Notch 1 and Hes 1 in cortical neurons were increased after RSV, but sharply decreased after DAPT treatment. Moreover, RSV increased brain-derived neurotrophic factor (BDNF) levels in cortical neurons, but in the culture medium, and the effect could be partially suppressed by DAPT treatment. : These findings indicate that RSV mediates neurite outgrowth in primary cortical neurons. The RSV-induced neuritogenic effect is mediated at least partly via the Notch1/BDNF pathway.
神经元的轴突生长对于形成功能性神经回路至关重要。据信，神经元轴突生长是脑可塑性的重要机制。瑞舒伐他汀（RSV）是一种相对较新的他汀类药物，可能具有神经保护特性。然而，RSV是否对皮质神经元的轴突延伸产生影响及其潜在机制仍鲜有文献记载。：采用免疫荧光法通过测量轴突长度来检测RSV对原代皮质神经元轴突生长的影响，并证实了其促进作用。然后，研究了涉及Notch1通路的潜在机制。使用qRT-PCR测定RSV对Notch 1和Hes1表达的影响。此外，还使用qRT-PCR和ELISA评估脑源性神经营养因子（BDNF）的表达。：RSV促进了皮质神经元的轴突生长，而Notch 1通路抑制剂DAPT可部分阻止这种作用。随后，我们发现Jagged 1和Notch 1共定位。此外，我们观察到RSV处理后皮质神经元中Notch 1和Hes 1的水平均升高，但DAPT处理后急剧下降。此外，RSV增加了皮质神经元中脑源性神经营养因子（BDNF）的水平，但在培养基中，且该作用可被DAPT处理部分抑制。：这些发现表明RSV介导原代皮质神经元的轴突生长。RSV诱导的轴突生成作用至少部分是通过Notch1/BDNF通路介导的。
