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

Aim: 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 (LIP) impairment in animal models of Alzheimer's disease. Methods: 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. LIP impairment was studied in the dentate region of A beta(1-42)-injected rats and APP/PS1 transgenic mice. Results: 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 mu mol/L, icv) did not change the basal synaptic transmission, but significantly enhanced the high-frequency stimulation (HFS)-induced LIP, which was completely prevented by pre-injection of APV (150 mu mol, icv). Chronic administration of dl-PHPB (100 mg.kg(-1).d(-1), po) reversed LIP impairment in A beta(1-42)-injected normal rats and APP/PS1 transgenic mice. Conclusion: Chronic administration of dl-PHPB improves learning and memory and promotes LIP in the animal models of Alzheimer's disease, possibly via increasing p-GluN2B expression in the hippocampus.