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P3‐056: Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice
Author(s) -
Abe Koji,
Kurata Tomoko,
Miyazaki Kazunori,
Kozuki Miki,
Morimoto Nobutoshi,
Ohta Yasuyuki,
Ikeda Yoshio,
Matsuura Tohru
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1495
Subject(s) - pitavastatin , atorvastatin , statin , endocrinology , medicine , cholesterol , neuroinflammation , amyloid precursor protein , pharmacology , senile plaques , chemistry , alzheimer's disease , inflammation , disease
Background: Presenilin 1 (PS1) mutations are responsible for many earlyonset familial Alzheimer’disease (FAD) cases. While increasing evidence points to impaired synaptic plasticity as an early event in AD, PS1 mutant mice exhibit a paradoxical increase in hippocampal early phase of LTP (E-LTP). Among PS1 mouse models, PS1 M146V knock-in mice (PS1KI) are particularly interesting in that they exhibit impairment in spatial tasks (Sun et al, 2005). Here we investigated the effects of aging on two forms of LTP in PS1KI mice, the widely studied E-LTP and a particular form of LTP called late-LTP (L-LTP), which requires transcription and protein synthesis. L-LTP, is thought to be critical for long-termmemory.Methods: Recording are from the cA1 region of hippocampal slices. Baseline fEPSPs was recorded during 30 min and L-LTP was recorded during 4 hours. ELTP and L-LTP were recorded from PS1KI and wild-type littermate control at the age of 3, 6, 9, and 12 months. All mice were maintained on an homogenous genetic background (C57BL/6). Results: At 3 month of age, we observed a larger L-LTP induction from than PS1KI than fromWT littermates during the first 30 min of recording. PS1KI mice exhibited a decrease in LLTP amintenance. At the same age, we observed an increase in the E-LTP in PS1KI mice compared toWTmice. From 6month of age to 12 month the LLTP was impaired thoughout the 4 hours of recording compred to WT. ELTP were still increased in 6 month old PS1KI compared to WT littermates. At 9 months of age, no significant difference was found between E-LTP of PS1KI and WT littermates. At 12 months of age, E-LTP was significantly decreased compare to WT littermates. Conclusions: We identify an early impairment of L-LTP maintenance which may explained the impairment in spatial memory induced by PS1 (M146V) KI mutation. The E-LTP is increased at an early stage, but decline at middle age (12 months).