title: Polygalasaponin F induces long-term potentiation in adult rat hippocampus via NMDA receptor activation.
abstract: OBJECTIVE
  To investigate the effect and underlying mechanisms of polygalasaponin F (PGSF), a triterpenoid saponin isolated from Polygala japonica, on long-term potentiation (LTP) in hippocampus dentate gyrus (DG) of anesthetized rats.
  
  
  METHODS
  Population spike (PS) of hippocampal DG was recorded in anesthetized male Wistar rats. PGSF, the NMDAR inhibitor MK801 and the CaMKII inhibitor KN93 were intracerebroventricularly administered. Western blotting analysis was used to examine the phosphorylation expressions of NMDA receptor subunit 2B (NR2B), Ca(2+)/calmodulin-dependent kinase II (CaMKII), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB).
  
  
  RESULTS
  Intracerebroventricular administration of PGSF (1 and 10 μmol/L) produced long-lasting increase of PS amplitude in hippocampal DG in a dose-dependent manner. Pre-injection of MK801 (100 μmol/L) or KN93 (100 μmol/L) completely blocked PGSF-induced LTP. Furthermore, the phosphorylation of NR2B, CaMKII, ERK, and CREB in hippocampus was significantly increased 5-60 min after LTP induction. The up-regulation of p-CaMKII expression could be completely abolished by pre-injection of MK801. The up-regulation of p-ERK and p-CREB expressions could be partially blocked by pre-injection of KN93.
  
  
  CONCLUSIONS
  PGSF could induce LTP in hippocampal DG in anesthetized rats via NMDAR activation mediated by CaMKII, ERK and CREB signaling pathway.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Chuang-jun
authors.initials: CJ
authors.lastname: Li
authors.forename: Yu-he
authors.initials: YH
authors.lastname: Yuan
authors.forename: Dong-ming
authors.initials: DM
authors.lastname: Zhang
authors.forename: Nai-hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation; D031801:Polygala / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D012503:Saponins; D014315:Triterpenes; C573752:polygalasaponin F; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases