title: Dehydroepiandrosterone sulfate prevents ischemia-induced impairment of long-term potentiation in rat hippocampal CA1 by up-regulating tyrosine phosphorylation of NMDA receptor.
abstract: We have reported that dehydroepiandrosterone sulfate (DHEAS) reduces the threshold for long-term potentiation (LTP) in Shaffer collateral-CA1 synapses through the amplification of Src-dependent NMDA receptor signaling. The present study is a follow-up of the above reports, aiming at evaluating the effects of DHEAS on the impaired LTP in reversible forebrain ischemic rats. Transient (20 min) incomplete forebrain ischemia led to an impaired LTP in the hippocampal CA1 region without damages to the basal synaptic transmission between the Shaffer collaterals and pyramidal neurons. Repetitive administrations of DHEAS (20 mg/kg for 3 days) from the first 3 h of reperfusion, but not acute DHEAS application (50 microM), prevent the impairment of LTP produced by ischemia. Co-administration of the specific sigma(1) receptor antagonist NE100 with DHEAS completely prevented the protective effect of DHEAS. In contrast, progesterone (PRGO) not only had no protective effect against the ischemic LTP impairment, but also attenuated the protective effect of DHEAS on the impaired LTP. Tyrosine phosphorylation of NMDA receptor subunit 2B (NR2B) significantly decreased after ischemia, whereas that of NR1 had no obvious change. Furthermore, the repetitive administration of DHEAS improved the reduction in tyrosine phosphorylation of NR2B. These findings suggest that the repetitive activation of sigma(1) receptor induced by DHEAS might prevent the ischemic LTP impairment through regulating the tyrosine phosphorylation of NR2B.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Hanzhong Road 140, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Shengzhong
authors.initials: S
authors.lastname: Cui
authors.forename: Guiqin
authors.initials: G
authors.lastname: Xie
authors.forename: Weiyan
authors.initials: W
authors.lastname: Cai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D047468:Immunoprecipitation / Q000379:methods; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000840:Anisoles; D018691:Excitatory Amino Acid Antagonists; D011437:Propylamines; D016194:Receptors, N-Methyl-D-Aspartate; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D004281:Docosahexaenoic Acids; D014443:Tyrosine; D019314:Dehydroepiandrosterone Sulfate; D015763:2-Amino-5-phosphonovalerate