title: Danggui-Jakyak-San enhances hippocampal long-term potentiation through the ERK/CREB/BDNF cascade.
abstract: BACKGROUND
  Danggui-Jakyak-San (DJS), a traditional herbal prescription, has long been used to treat gerontological disorders due to insufficient blood supply.
  
  
  OBJECTIVE
  Previously, we reported that DJS increased hippocampal neurogenesis and enhanced learning and memory. However, the precise mechanism of DJS and its effects on learning and memory are still not well understood. In this study, we investigated the effect of DJS on hippocampal long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory.
  
  
  METHODS
  To understand the effect of DJS on LTP, we used acute mouse hippocampal slices and delivered one train of high frequency stimulation (100 Hz, 100 pulses). Western blots were used to analyze the changes in protein levels induced by DJS. Morris water maze test was used to evaluate the effect of DJS on spatial long-term memory.
  
  
  RESULTS
  DJS enhanced LTP in the Schaffer-collateral pathway of the hippocampus in a concentration-dependent manner. Extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) were activated by DJS. Moreover, brain-derived neurotropic factor (BDNF) was also increased by DJS. Blockade of ERK1/2 activation with PD198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LTP enhancement. In vivo, DJS improved spatial long-term memory and upregulated the hippocampal CREB/BDNF cascade.
  
  
  CONCLUSIONS
  These results suggest that DJS enhances hippocampal LTP and spatial memory through the ERK/CREB/BDNF cascade.
authors.affiliation: School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Yi
authors.affiliation: Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University, Busan, Republic of Korea.
authors.lastname: Hye Jin Park
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Jebong-ro, Gwangju 501-757, Republic of Korea.
authors.forename: Soo Ji
authors.initials: SJ
authors.lastname: Beak
authors.affiliation: Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Seungheon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University, Kyungsan, Republic of Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Jung
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Jebong-ro, Gwangju 501-757, Republic of Korea.
authors.forename: Byeong C
authors.initials: BC
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and,College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University, Busan, Republic of Korea. Electronic address: mose79@dau.ac.kr.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; C413220:toki-shakuyaku-san; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 10-DEBC hydrochloride (PubChem CID: 16760284); Danggui-Jakyak-San; ERK1/2; Hippocampus; K252a (PubChem CID: 490561); Long-term potentiation; Morris water maze; PD198306 (PubChem CID: 9956637)