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Potassium 2-(1-hydroxypentyl)-benzoate promotes long-term potentiation in Aβ1-42-injected rats and APP/PS1 transgenic mice.

ABSTRACT: Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a new drug candidate for ischemic stroke. The aim of this study was to investigate the effects of dl-PHPB on memory deficits and long-term potentiation (LTP) impairment in animal models of Alzheimer's disease.The expression of NMDA receptor subunits GluN1 and GluN2B in the hippocampus and cortex of APP/PS1 transgenic mice were detected using Western blot analysis. Memory deficits of the mice were evaluated with the passive avoidance test. LTP impairment was studied in the dentate region of Aβ1-42-injected rats and APP/PS1 transgenic mice.APP/PS1 transgenic mice showed significantly lower levels of GluN1 and p-GluN2B in hippocampus, and chronic administration of dl-PHPB (100 mg · kg(-1) · d(-1), po) reversed the downregulation of p-GluN2B, but did not change GluN1 level in the hippocampus. Furthermore, chronic administration of dl-PHPB reversed the memory deficits in APP/PS1 transgenic mice. In the dentate region of normal rats, injection of dl-PHPB (100 μmol/L, icv) did not change the basal synaptic transmission, but significantly enhanced the high-frequency stimulation (HFS)-induced LTP, which was completely prevented by pre-injection of APV (150 μmol/L, icv). Chronic administration of dl-PHPB (100 mg · kg(-1) · d(-1), po) reversed LTP impairment in Aβ1-42-injected normal rats and APP/PS1 transgenic mice.Chronic administration of dl-PHPB improves learning and memory and promotes LTP in the animal models of Alzheimer's disease, possibly via increasing p-GluN2B expression in the hippocampus.

SUBMITTER: Li PP

PROVIDER: S-EPMC4088280 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Synaptic changes in the dentate gyrus of APP/PS1 transgenic mice revealed by electron microscopy.

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RNA-seq of hippocampal samples from IL-18KO/APP/PS1 , WT, IL-18KO, and APP/PS1 mice.

Project description:The goal of the experiment was to understand the role of IL-18 in Alzheimers disease. Gene expression was examined in the hippocampus of wild type mice and the APP/PS1 mice (which are a mouse model for Alzheimers disease) that either encoded IL-18 or had the IL-18 gene knocked out.

2017-12-31 | E-MTAB-5668 | biostudies-arrayexpress

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