• Shun-Chang Fang, Hang Xie, Fang Chen, Mei Hu, Yan Long, Hong-Bin Sun, Ling-Yi Kong, Hao Hong, and Su-Su Tang.
• Department of Pharmacology, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
• Neuroscience. 2017 Jul 4; 355: 200-211.

AbstractDiabetes comes with an additional burden of moderate to severe hyperlipidemia, but little is known about the effects of lipid-lowering therapy on diabetic complications such as diabetes-associated cognitive decline. Herein we investigated the effects of statins on memory impairment and neurotoxicity in streptozotocin-induced diabetic mice. Our data indicated that oral administration of simvastatin at 10 or 20mg/kg for 4weeks significantly ameliorated diabetes-associated memory impairment reflected by performance better in the Morris water maze and Y-maze tests. The further study showed that these treatments caused significant increase of peroxisome proliferator-activated receptors gamma and decrease of NF-κB p65 in nucleus of hippocampus and cortex, and ameliorated neuroinflammatory response as evidenced by less Iba-1-positive cells and lower inflammatory mediators including IL-1β, IL-6 and TNF-α as well as suppressed neuronal apoptosis as indicated by decreased TUNEL-positive cells, increased ratio of Bcl-2/Bax and decreased caspase-3 activity in the hippocampus and cortex. Moreover, simvastatin pronouncedly attenuated amyloidogenesis by decreasing amyloid-β, amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1. As expected, treated with simvastatin, the diabetic mice exhibited significant improvement of hyperlipidemia rather than hyperglycemia. Our findings disclosed novel therapeutic potential of simvastatin for the diabetes-associated cognitive impairment.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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