Simvastatin attenuates aluminium chloride-induced neurobehavioral impairments through activation of TGF-β1/SMAD2 and GSK3β/β-catenin signalling pathways

Alzheimer's disease (AD) is a neurodegenerative disease characterised by the presence of beta-amyloid plaques and acetylcholine depletion leading to neurobehavioral defects. AD was contributed also with downregulation of TGF-beta 1/SMAD2 and GSK3 beta/beta-catenin pathways. Simvastatin (SMV) improved memory function experimentally and clinically. Hence, this study aimed to investigate the mechanistic role of SMV against aluminium chloride (AlCl3) induced neurobehavioral impairments. AD was induced by AlCl3 (50 mg/kg) for 6 weeks. Mice received Simvastatin (10 or 20 mg/kg) or Donepezil (3 mg/kg) for 6 weeks after that the histopathological, immunohistochemical and biochemical test were examined. Treatment with SMV improved the memory deterioration induced by AlCl3 with significant recovery of the histopathological changes. This was concomitant with the decrease of AChE and A beta((1-42)). SMV provides its neuroprotective effect through upregulating the protein expression of beta-catenin, TGF-beta 1 and downregulating the expression of GSK3 beta, TLR4 and p-SMAD2.