Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus.
Docosahexaenoic acid (DHA) has been suggested to be required for neuronal development and synaptic plasticity. However, in view of the fact that DHA facilitates NMDA responses and blocks K(+) channels, it might predispose the neurons to epileptiform bursting. By using extracellular recording of population spikes in the CA1 region of rat hippocampal slices, we tested this possibility by examining the effect of DHA on the epileptiform activity induced by bicuculline or in Mg(2+)-free medium. When stimuli were delivered to the Schaffer collateral/commissural pathway every 20 or 30 sec, DHA had no significant effect on the epileptiform activity. However, when the frequency of stimulation was increased to 0.2 Hz, DHA attenuated the amplitude of the bursting activity induced by bicuculline to 57.5+/- 10.8% and those induced by Mg(2+)-free ACSF to 65.8+/-13.9% of control. DHA reduced the slope of field excitatory postsynaptic potential (fEPSP) to 77.1+/-7.4% of baseline, without significant effect on the ratio of paired-pulse facilitation (PPF). By intracellular recording of neurons in the stratum pyramidale of rat hippocampal slices, we found that DHA markedly inhibited the repetitive firing of action potentials elicited by depolarizing current pulses but did not affect the initial action potential. Thus, DHA may attenuate epileptic activity mainly through the frequency-dependent blockade of Na(+) channels.
Young
C
C
Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Gean
P W
PW
Chiou
L C
LC
Shen
Y Z
YZ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D003292:Convulsants; D004281:Docosahexaenoic Acids; D008274:Magnesium; D001640:Bicuculline