Atorvastatin improves long-term memory by reducing amyloid-β formation and neuronal damage in STZ-induced diabetic rats

Abstract

Diabetes mellitus is associated with decline in cognitive function and changes in brain structure. Statins have received increasing attention to be used as neuroprotective drug. We examined the neuroprotective effects of atorvastatin on neuropathological alterations such as learning and memory performance, the amyloid-beta formation, and expression of nitric oxide synthases (NOSs) in hippocampus of streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were divided into four groups; The normal control group, STZ-induced diabetes group, STZ-induced diabetic rats followed by treatment with atorvastatin group and normal rats treated with atorvastatin. The passive avoidance test was used to evaluate the learning and memory status of animals. Blood and hippocampus samples were obtained for biochemical and histological analysis. The expressions of nitric oxide synthases were immunohistochemically detected, and histopathological changes of amyloid beta were examined using Congo red stain in CA1 region of hippocampus. Count of congo red positive cells in CA1 region increased in diabetic rats, however atorvastatin treatment decreased it. Amyloid-beta levels and S100B levels in the hippocampus and plasma increased in diabetic rats, atorvastatin treatment decreased. Total nitrite-nitrate levels increased, while iNOS expression decreased in the CA1 area of hippocampus in atorvastatin treated diabetic rats, eNOS and nNOS expression increased. The retention latency times of diabetes group decreased, however atorvastatin treatment to diabetic rats prolonged at the 48th hour and 72nd hour. Atorvastatin improved the long-term memory by suppressing the formation of amyloid-beta, increasing eNOS and nNOS protecting the blood brain barrier in diabetic rats.