Epidemiological and animal studies increasingly recognize the harmful effects of ionizing radiation, even at low doses. Such health effects not only entail the increased risk of developing cancer, but also include non-cancer effects. Intriguingly, long-term radiation-induced changes seem to share several similarities with ageing, defined by chronic oxidative stress, apoptosis, inflammation, and genetic instability among others. Indeed, an association between radiation exposure and ageing or premature senescence is now evidenced and becoming well documented (Hernandez et al., 2015). As ageing is often accompanied with a loss of memory, dementia and a higher risk of developing neurodegenerative diseases such as Alzheimer disease (AD), a strong interest in studying the effect of radiation on ageing of the brain is emerging. For example, cognitive impairment and dementia is commonly observed in patients that received cranial radiotherapy earlier in life (Zhang et al., 2015), while animal data could corroborate a premature senescence, defined by chronic oxidative stress and inflammation, in irradiated brain tissue (Suman et al., 2013; Poulose et al., 2011). Interestingly, a study by Lowe et al. (2009) and results obtained at SCK•CEN (Verreet et al., unpublished data) suggested remarkable similarities in transcriptional response in the ageing and irradiated mouse brain, and proposed a potential link with AD-related genes.
Despite the current awareness, major drawbacks in this field are the inconclusive epidemiological data, probably resulting from the lack of large-scale studies, and the insufficient knowledge on low-dose radiation exposure, which is a growing health concern for our society. Besides, the effect of radiation to the developing brain, for example during early childhood, remains largely elusive and needs to be actively explored. Therefore, this project will focus on different radiation doses, ranging from low-dose diagnostic to high-dose radiotherapy doses, administered to young mice predisposed to developing an AD-like phenotype, after which various ageing parameters will be investigated via a multidisciplinary approach.
Hernandez, L., M. Terradas, J. Camps, M. Martin, L. Tusell and A. Genesca (2015). "Aging and radiation: bad companions." Aging Cell 14(2): 153-161
Lowe, X. R., S. Bhattacharya, F. Marchetti and A. J. Wyrobek (2009). "Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease." Radiat Res 171(1): 53-65.
Poulose, S. M., D. F. Bielinski, K. Carrihill-Knoll, B. M. Rabin and B. Shukitt-Hale (2011). "Exposure to 16O-particle radiation causes aging-like decrements in rats through increased oxidative stress, inflammation and loss of autophagy." Radiat Res 176(6): 761-769.
Suman, S., O. C. Rodriguez, T. A. Winters, A. J. Fornace, Jr., C. Albanese and K. Datta (2013). "Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production." Aging (Albany NY) 5(8): 607-622.
Zhang, L., H. Yang and Y. Tian (2015). "Radiation-induced cognitive impairment." Therapeutic Targets for Neurological Diseases 2(2).