Rosuvastatin improves neurite extension in cortical neurons through the Notch 1/BDNF pathway.

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

DISCUSSION: 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.