• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Trophic Factors

開催日 2014/9/12
時間 18:10 - 19:10
会場 Room J(313+314)
Chairperson(s) 小島 正己 / Masami Kojima (独立行政法人産業技術総合研究所 健康工学研究部門 バイオインターフェース研究グループ / Biointerface Research Group, Health Research Institute (HRI), National Institute of Advanced Industrial Science and Technology (AIST), )
篠田 陽 / Yo Shinoda (東京理科大学理工学部 応用生物科学科 / Deparment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Japan)

Reduction of Plasmalogens in the Mice Hippocampus Significantly Reduces the Memory by Downregulating BDNF and its Target Gene Expressions

  • O2-J-6-1
  • 片渕 俊彦 / Toshihiko Katafuchi:1 Hossain Shamim Md. / Shamim Md. Hossain:1 Ahmed Saleh Md. Youss / Saleh Md. Yous Ahmed:1 三明 清隆 / Kiyotaka Miake:2 
  • 1:九州大院・医・統合生理学分野 / Dept Integr Physiol, Grad Sch Med Sci, Kyushu Univ., Fukuoka Japan 2:丸大食品(株)中央研究所 / Center Research Institute, Marudai Food Company Lit., Osaka, Japan 

Plasmalogens (Pls) are unique glycerophospholipids containing a vinyl ether bond at the sn-1 position of the glycerol backbone, which are not only structural membrane components and reservoirs for second messengers, but they are also involved in membrane fusion, ion transport and cholesterol efflux. It has been well known that our brain, especially the hippocampus, contains a large amount of ethanolamine plasmalogens (EthPls) and previous reports in the Alzheimer's disease (AD) patients have shown that Pls are reduced in the brain tissues suggesting a role of Pls in the memory. We therefore, performed memory test with the mice that contained reduced Pls in the hippocampus. To knock down the Pls in the hippocampus, we have designed short hairpin RNAs (sh-RNAs) based on lentivirus vectors against the two major enzymes GNPAT (glyceronephosphate O-acyltransferase) and AGPS (alkylglyceronephosphate synthase) necessary for the de novo synthesis of Pls. These lentiviruses effectively reduced the expression of GNPAT and AGPS in the cells and also in the hippocampal tissues. For the behavioral study, we injected the lentiviruses at the dose of (5X105 transduction unit) into the hippocampus directly by stereotaxic instrument. Morris water navigation task showed a significant reduction in the memory from first week to the 5th weeks of the injection in Pls knock-down mice. In addition we found a significant reduction in the expression of brain derived neurotrophic factor (BDNF) and its target genes Synapsin-1 and Synaptotagmin-1 in the Pls knock-down hippocampus as well as Neuro-2A cell line. Furthermore, the mice receiving Pls-containing diet for 6 weeks showed increase Pls content in hippocampus and memory enhancement in Morris water maze test, which was blocked by knock-down of BDNF gene. Our present study confirms for the first time that the endogenous Pls in the hippocampus are very important to maintain our memory via regulating the expression of BDNF and its related genes.

Copyright © Neuroscience2014. All Right Reserved.