title: Neuroprotective actions of eicosapentaenoic acid on lipopolysaccharide-induced dysfunction in rat hippocampus.
abstract: Eicosapentaenoic acid (EPA) protects hippocampus from age-related and irradiation-induced changes that lead to impairment in synaptic function; the evidence suggests that this is due to its anti-inflammatory effects, specifically preventing changes induced by the proinflammatory cytokine, interleukin-1beta (IL-1beta). In this study, we have investigated the possibility that EPA may prevent the effects of lipopolysaccharide (LPS) administration, which have been shown to lead to deterioration of synaptic function in rat hippocampus. The data indicate that treatment of hippocampal neurones with EPA abrogated the LPS-induced increases in phosphorylation of the mitogen-activated protein kinase, c-Jun N-terminal kinase (JNK), the transcription factor, c-Jun and the mitochondrial protein, Bcl-2. In parallel, we report that intraperitoneal administration of LPS to adult rats increases phosphorylation of JNK, c-Jun and Bcl-2 in hippocampal tissue and that these changes are coupled with increased IL-1beta concentration. Treatment of rats with EPA abrogates these effects and also blocks the LPS-induced impairment in long-term potentiation in perforant path-granule cell synapses that accompanies these changes. We propose that the neuroprotective effect of EPA may be dependent on its ability to inhibit the downstream consequences of JNK activation.
authors.affiliation: Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lonergan
authors.forename: Darren S D
authors.initials: DS
authors.lastname: Martin
authors.forename: David F
authors.initials: DF
authors.lastname: Horrobin
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001927:Brain Diseases / Q000139:chemically induced / Q000517:prevention & control*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000293:injuries / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D017774:Long-Term Potentiation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D015118:Eicosapentaenoic Acid; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases