Lovastatin attenuates NMDA induced excitotoxicity in rat cortical neurons

Objective To observe the effect of lovastatin on NMDA induced excitotoxicity in rat cortical neurons.Methods Cortical neurons were prepared from E17 rat.Cell viability was evaluated with typan blue dye exclusion test,apoptosis was detected with TUNEL staining,and the morphology and number of neurons was assessed with MAP-2 immunofluorescence staining.Results Typan blue staining demonstrated that 500 nmol/L lovastatin pre-treatment 3d significantly and selectively protected neurons against NMDA induced excitotoxicity but not against staurosporine induced apoptosis.The protective effects were completely abolished co-treated with lovastatin and MVA,indicating protection was dependent on cholesterol-lowering.Moreover,protection of lovastatin was dosage-and time-dependent.In line with this evidence,lovastatin decreased apoptosis upon NMDA by TUNEL staining.Immunofluorescence staining demonstrated the number of MAP-2 positive neurons decreased and survival neurons showed a loss of MAP-2 positive dendrites after NMDA treatment,which were not visible after lovastatin pre-treatment.Conclusions Lovastatin significantly and selectively attenuated NMDA induced excitotoxicity,indicating that lovastatin has potential neuroprotective effects on excitotoxicity-related neuropathology.