The effect of simvastatin and rosuvastatin on relieving the symptoms of alzheimer's disease in a mouse model

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia affecting nearly 36million people globally. None of the currently approved drugs prevent or even slow the course of the disease. Objective: To investigate effects of simvastatin and rosuvastatin in relieving symptoms of AD in mice. Methods: The design was experimental using a mice model. A total of 72 Balbc male mice aged 8-12 weeks were divided into 9 groups with 8 mice in each group. Scopolamine 1mg/kg/day was given intraperitoneally over a period of 2 weeks to induce AD. Study groups were control, simvastatin 5mg/kg/day, simvastatin 10mg/kg/day, simvastatin 20mg/kg/day, rosuvastatin 10mg/kg/day, rosuvastatin 20mg/d/day, rosuvastatin 40mg/kg/day and donepezil 5mg/kg/day administered by oral gavage for 2 weeks. Y-maze to assess short term memory and Novel Object Recognition test to assess cognition, short-term, intermediate and long-term memory were administered starting 24 hours after the last dose of the experimental drugs. Parametres assessed with Y-maze were total arm entries, same arm entries, alternate arm entries, percentage spontaneous arm alternations. Data were analysed using One way or Two way ANOVA with an appropriate post hoc where required. An a priori alpha level of 0,05 was set for all statistical analysis. Results: All 8 mice in simvastatin 20mg/kg group died therefore this group was excluded from statistical analysis. There was no significant difference in the parameters used in the Y-maze test across all treatment groups. Total Arm Returns (F=0.5708, d.f. = 6; 28, p= 0,9396), Same Arm Returns (F= 0.4762, d.f= 6; 28, p=0.820), Alternate Arm Returns (F=0.4272, d,f 6,28, p= 0,8545) and percentage spontaneous alternation ( F=0,2911, d,f= 6,28, p= 0.9361). Similarly, no significant difference were noted in the time spent exploring familiar objects across the experimental groups (F=0.4578, d.f=6;28, p=0.7453). However, significant differences were noted on the time spent exploring novel objects across the treatment groups (F=5.755, d,f= 6,28, p= 0.0005). The discrimination indices were found to be different between groups (F= 8.031, d,f= 6,28, p< 0,001; Kruscal-Wallis test .2= 20,46; p=0,0023. Conclusion: Repeated dosing of simvastatin and rosuvastatin had no effect on memory in mice. No dose response relationship in reversing symptoms of AD with these statins was observed.