Research About Rapid Alterations Of Epigenetics In The Hippocampus Of Rat After Whole Brain Irradiation

Purpose To investigate the role of epigenetic in the irradiation-induced memory deficiency by observing the changes of histon H3 acetylation and DNA methylation in the hippocampus of rat brain radiation injury model.Materials and methods Young adult, male Sprague-Dawley rats (150–200 g,4-5 weeks) were divided into groups of 2Gy, 30Gy, and control. After whole brain irradiation, the total protein was extracted from irradiated hippocampus and whole brain 30μm cryosections were cut coronally through the center of the impact using a Leica cryostat at 7 days and 30 days. Western blot was performed and the brain sections were immunohistochemiea stained. The alterations of histon H3 acetylation and DNMTs was observed and analyzed.Results We show that both 2Gy and 30 Gy 4MV nominal photon energy lead to significent deacrease in histon H3 acetylation in the hippocampus. We found a 25% reduction in histon H3 acetylation at 7 days (P < 0.05) and 5% reduction at 30 days (P < 0.05) after 2Gy irradiation. Campared to control, 30Gy induced 13% reduction at 30 day but 5% reduction at 7 day. In the early stage, low-dose induced more significant epigenetic alterations. 2Gy and 30 Gy irradiation induced the increase of DNMT1 (P < 0.05) and decrease of DNMT3b (P < 0.05), DNMT3a was not impaired.Conclusion Decreased histone H3 acetylation and the alterations of DNMTs suggest altered hippocampal epigenetic signaling after whole brain irradiation. This result indicate that alterations in chromatin structure may be a new possible molecular correlate of irradiation-induced memory deficiency.