Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Abstract

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.

Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway

“…However, few studies reported the involvement of MAPKs in the process. Two studies from the same group revealed that radiation activated JNK in the hippocampus and induced apoptosis, with the main focus on neuronal cell death (Lonergan et al, 2002;Lynch et al, 2003). In line with these studies, we have clearly demonstrated that JNK mediated radiation-induced apoptosis in NSCs.…”

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

“…Cell biological and molecular studies suggest that omega-3 fatty acids modulate membrane fluidity (Hashimoto et al, 1999), dopaminergic (Piomelli, 1994) and serotonergic (Yao et al, 2004) neurotransmission, and differentially alter gene expression (Kitajka et al, 2002;Salvati et al, 2004). Furthermore, preclinical studies suggest that omega-3 fatty acids have neuroprotective properties Lynch et al, 2007;Martin et al, 2002). Animal and human studies provide ample evidence that essential fatty acid deprivation during pregnancy is associated with developmental and behavioral abnormalities (Innis et al, 1999;Wainwright et al, 1994a, b) that are ameliorated by essential fatty acid supplementation (Helland et al, 2003;Wainwright et al, 1994a, b).…”

Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation

“…45 Recently, it has been shown that the essential fatty acid precursor eicosapentaenoic acid reduced ROS levels and resulted in less radiation-induced injury in the adult rat brain. 17 Hq mice are more susceptible to oxidative stress, 32,34 but the free radical scavenger edaravone did not provide any beneficial effects, as judged by the SVZ size reduction 7 days after IR. This stands in contrast to a study showing in vivo The SVZ areas in Wt, Het and Hq mice were measured in the contra-and ipsilateral hemispheres 7 days after IR.…”

“…However, no effective methods for protecting the normal brain tissue have been established and there is a lack of animal models investigating strategies to limit the debilitating effects of cranial RT. [14][15][16][17][18][19] Neurogenesis occurs throughout life in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus, [20][21][22] making them particularly susceptible to IR-induced apoptosis. 14,15,23,24 Therapeutic doses of irradiation (IR) result in increased apoptosis, 23,25 decreased cell proliferation and reduced stem/progenitor cell differentiation into neurons within the neurogenic regions, both in rodents 24,26 and in humans.…”