Abstract
Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion 56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation.
Highlights
Radiation exposure to normal brain tissue during therapeutic and diagnostic procedures is unavoidable and radiation has been shown to affect brain function [1,2,3]
reactive oxygen species (ROS) levels were distinctly increased in freshly isolated cerebral cortical cells two and twelve months after exposure to 1.6 Gy of 56Fe radiation compared to shams and 2 Gy γirradiated samples. (Figure 1A, B, D, and E)
Radiation exposure on one hand has been reported to induce long-term changes in central nervous system (CNS) resulting in functional impairments such as motor and sensory disturbances, and learning and memory deficits [61,62] and on the other it has been associated with risk of initiation and promotion of brain tumor [7,8,63]
Summary
Radiation exposure to normal brain tissue during therapeutic and diagnostic procedures is unavoidable and radiation has been shown to affect brain function [1,2,3]. Important advances have been made in the field of radiation therapy to make it more focused, radiation exposure to normal brain tissue is inescapable leading to long-term functional deficit such as cognitive, visual, and motor impairments. A single head and neck CT scan, depending on age, could expose brain to radiation doses between 20 and 100 mGy and with marked increase in radiation based diagnostic procedures [5,6,7], the cumulative radiation dose to brain due to repeated exposure could be high enough to raise long-term health concern such as functional decline and cancer [8]. Epidemiological studies in atom bomb survivors have shown increased cancer risk after www.impactaging.com
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