Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin-induced diabetic mice

Neuroscience
Shun-Chang FangSu-Su Tang

Abstract

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....Continue Reading

Citations

May 28, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Devin WahlDavid G Le Couteur
Feb 27, 2020·International Journal of Molecular Sciences·Yu-Chia KaoKuen-Jer Tsai
Jan 14, 2021·International Immunopharmacology·Shahab GhaderiKhodabakhsh Rashidi

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