Neuroprotective effect of eicosapentaenoic acid in hippocampus of rats exposed to gamma-irradiation.
Exposure to irradiation leads to detrimental changes in several cell types. In this study we assessed the changes induced in hippocampus by exposure of rats to whole body irradiation; the findings reveal that irradiation leads to apoptotic cell death in hippocampus, and as a consequence, long term potentiation in perforant path-granule cell synapses is markedly impaired. The evidence is consistent with the view that irradiation induced an increase in reactive oxygen species and that this leads to stimulation of the stress-activated protein kinase, JNK, and activation of the transcription factor, c-Jun. Consequent upon activation of JNK, a cascade of cell signaling events was stimulated that ultimately resulted in apoptosis, as suggested by parallel increases in cytochrome c translocation, caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and terminal dUTP nick-end labeling staining. Treatment of rats with eicosapentaenoic acid inhibited the irradiation-induced increase in reactive oxygen species production and the subsequent cellular signaling events, suggesting that oxidative stress triggered apoptotic cell death in the hippocampus of rats exposed to irradiation. Significantly, when the compromise in cell viability induced by irradiation was prevented by eicosapentaenoic acid, long term potentiation was sustained in a manner similar to that in the sham-treated control group.
Lonergan
Peter E
PE
Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin 2, Ireland.
Martin
Darren S D
DS
Horrobin
David F
DF
Lynch
Marina A
MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003574:Cytochrome c Group; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005720:Gamma Rays; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases; D017774:Long-Term Potentiation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species
D003574:Cytochrome c Group; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D015118:Eicosapentaenoic Acid; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases