Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin-induced diabetic mice.
Diabetes 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.
['Fang|Shun-Chang|SC|', 'Xie|Hang|H|', 'Chen|Fang|F|', 'Hu|Mei|M|', 'Long|Yan|Y|', 'Sun|Hong-Bin|HB|', 'Kong|Ling-Yi|LY|', 'Hong|Hao|H|', 'Tang|Su-Su|SS|']
D053829:Amyloid Precursor Protein Secretases D016229:Amyloid beta-Peptides D016564:Amyloid beta-Protein Precursor D000818:Animals D016282:Aspartic Acid Endopeptidases D001786:Blood Glucose D001921:Brain D016207:Cytokines D003921:Diabetes Mellitus, Experimental D004195:Disease Models, Animal D000960:Hypolipidemic Agents D008297:Male D018782:Maze Learning D008569:Memory Disorders D051379:Mice D008813:Mice, Inbred ICR D020258:Neurotoxicity Syndromes D010446:Peptide Fragments D015398:Signal Transduction D019821:Simvastatin
simvastatin memory diabetes neuronal apoptosis amyloidogenesis neuroinflammation