Comparative impact of fractionated and acute doses of gamma irradiation on the rats' brain after whole body irradiation.

Abstract

Purpose: Understanding the distinct impacts of fractionated versus acute doses of whole body irradiation on the brain and how these contrasting dosing schedules affect the brain at a cellular and molecular level.

Materials and methods: Thirty healthy rats (males) were separated into five groups. Groups I, III, and V were irradiated by 0 Gy, 6 Gy, and 8 Gy of whole body γ-irradiation, respectively. Groups II and IV were irradiated by 6 Gy and 8 Gy as fractionated doses/4 (24-hour interval), respectively. Twenty-four hours after irradiation the total antioxidant capacity (TAC), comet assay, phosphorylated tau (p-tau) protein, caspase-3, transforming growth factor-β (TGF-β), microtubule-associated protein tau (MAPT) and protein kinase-N (PKN) gene expressions, and doublecortin (DCX) were measured.

Results: The present study indicated varying levels of TAC, DNA damage, p-tau, caspase-3, and DCX, based on the dosing strategy employed. Acute doses resulted in greater DNA damage and early molecular indicators associated with neurodegenerative pathway compared to fractionated doses. Changes in PKN and MAPT gene expressions were also observed, suggesting genetic responses to radiation exposure; however, the acute irradiation did not significantly induce the gene expression changes compared to the respective fractionated group. In a different manner, TGF-β at (8 Gy) showed significant unique decrease in contrast to the substantial increase after exposure to (8 Gy/4) irradiation.

Conclusions: There is a potential effect of the dosing strategy on brain's antioxidant defense system's response to oxidative stress, DNA, apoptotic pathway, neuronal function and structure, and neurogenesis. TGF-β results underscore its signaling in mediating the brain's response to irradiation-induced damage.