Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A(2) inhibitor in rat hippocampal slices.
1. We investigated the possible involvement of phospholipase A(2) (PLA(2)) and its products in long-term potentiation (LTP) in the CA1 neurotransmission of rat hippocampal slices. 2. Inhibitors of Ca(2+)-independent PLA(2) (iPLA(2)) prevented the induction of LTP without affecting the maintenance phase of LTP whereas Ca(2+)-dependent PLA(2) inhibitors were virtually ineffective, which suggests a pivotal role of iPLA(2) in the initiation of LTP. 3. We then investigated the effect of docosahexaenoic acid (DHA) and arachidonic acid (AA) on BEL (bromoenol lactone, an iPLA(2)-inhibitor) -impaired LTP, and found that either DHA or AA abolished the effect of BEL. However, DHA did not restore BEL-attenuated LTP when applied after the tetanus. DHA per se affected neither the induction nor maintenance of LTP. Linoleic acid had no effects, either. 4. These results suggest that DHA is crucial for the induction of LTP and that endogenously released DHA during tetanus is sufficient to trigger the formation of LTP.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
S
S
Fujita
Y
Y
Ikegaya
M
M
Nishikawa
N
N
Nishiyama
N
N
Matsuki
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001095:Arachidonic Acids; D009281:Naphthalenes; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; C104810:methyl arachidonylfluorophosphonate; C081565:arachidonyltrifluoromethane; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A