Referenced in: none

Automatically associated channels: Slo1 , TASK1

Title: Simvastatin exerts antiamnesic effect in Aβ25-35 -injected mice.

Authors: Wen-Hong Zhi, Yan-Ying Zeng, Zi-Hong Lu, Wei-Jun Qu, Wei-Xian Chen, Lei Chen, Ling Chen

Journal, date & volume: CNS Neurosci Ther, 2014 Mar , 20, 218-26

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24289538

Abstract
Simvastatin (SV) is reported to improve cognition and slow the progression of Alzheimer's disease (AD). This study explored the mechanisms underlying the antiamnesic effect of SV in AD using behavior tests, histological examination, western blot analysis, and electrophysiological recording technique in AD model mice created by intracerebroventricular injection (i.c.v.) of Aβ25-35 .Chronic administration of SV (40 mg/kg/day) for 11 days after Aβ25-35 -injection ameliorated the impairment of acquisition performance and probe trail test in Morris water maze task and alternation behavior in Y maze task in Aβ25-35 -mice. Aβ25-35 -induced apoptosis of hippocampal CA1 pyramidal cells and Aβ25-35 -impaired high-frequency stimulation (HFS)-dependent long-term potentiation (LTP) induction in hippocampal Schaffer collaterale-CA1 synapse were rescued by SV-treatment. SV prevented Aβ25-35 -inhibited protein kinase B (Akt) and extracellular signal-related kinase-2 (ERK2) phosphorylation, which was sensitive to α7 nicotinic acetylcholine receptor (α7nAChR) antagonist MLA. SV-induced neuroprotection was attenuated by MLA or phosphatidylinositol-3-kinase (PI3K) antagonist LY294002. SV-rescued LTP induction was blocked by α7nAChR, PI3K or MAPK/ERK kinase (MEK) antagonist. Finally, the antiamnesia of SV in Aβ25-35 -mice was attenuated by blockage of SV-induced neuroprotection or SV-rescued LTP induction.The antiamnesia of SV in Aβ25-35 -mice depends on its neuroprotection and synaptic plasticity improvement.