Objective  To investigate the effect of simvastatin (SV) on the expression of synaptophysin (SYP) in cerebral cortex of cultured rats in vitro and its signal transduction mechanism.

  Methods  Neurons were isolated and cultured from cerebral cortex of neonatal Sprague Dawley rats. After 4 days, the rats were divided into control group, SV group (processed with 2, 4, 8 μmol/L SV for 48 h), PD98059 treatment group, and SV combined with PD98059 treatment group (firstly processed with 10 μmol/L blocker PD98059 for 30 min, and then treated with 10 μmol/L SV for 48 h). The expression of SYP was detected by immunofluorescence assay, and the levels of phosphorylated mitogen-activated protein kinase (p-MEK), phosphorylated extracellular regulated protein kinase 1 (p-ERK1) and phosphorylated extracellular regulated protein kinase 2 (p-ERK2) were detected by Western blot.

  Results  Immunofluorescence assay showed that 4 μmol/L SV could significantly enhance the immunoreactivity of SYP. Western blot showed that 8 μmol/L SV could significantly increase the levels of SYP, p-MEK, p-ERK1 and p-ERK2. PD98059 can significantly reduce up-regulation of SYP, p-MEK, p-ERK1 and p-ERK2 induced by SV.

  Conclusion  SV can up-regulate SYP expression by activating MEK/ERK signal transduction pathway.