title: Potassium 2-(1-hydroxypentyl)-benzoate promotes long-term potentiation in Aβ1-42-injected rats and APP/PS1 transgenic mice.
abstract: OBJECTIVE
  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.
  
  
  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. LTP impairment was studied in the dentate region of Aβ1-42-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 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Li
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Xu
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D019817:Benzoic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010420:Pentanes / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: C511222:2-(1-hydroxypentyl)-benzoate; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001565:Benzoates; D010420:Pentanes; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D019817:Benzoic Acid