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Ostinato - Acceleration of Parkinson pathogenesis by chronic low-dose rate gamma exposure

Tildelt: kr 0,39 mill.

Health risks of radiation exposure are of particular concern to the public, as highlighted by the challenges from the Fukushima accident. Although it is well established that ionising radiation can increase the risk of cancer, in recent years there has been an increased focus on the potential for radiation to cause late neurodegenerative diseases. The objective of the Ostinato project was to investigate the impact of in utero chronic low dose radiation on the development of Parkinson's disease. As a collaboration between Norway and Germany, more than 200 mice that had been specially breed to be susceptible to Parkinson's disease, together with wild type mice, were subject to controlled irradiation at the FIGARO low dose irradiation facility at NMBU. The offspring of the mice have been subject to a series of behavioural and molecular biology tests, and will be followed for another two years. To date there has been no evidence that ionizing radiation has increased the incidence of Parkinsons disease, although preliminary results suggested a possible impact on learning development. In addition to cognitive development, the study also included tests on a range of other biological endpoints in irradiated animals, and results confirmed a number of genotoxic effects of ionizing radiation. The study also resulted in improvement of the logistics and dosimetry for rodent irradiation experiments at the FIGARO irradiation facility.

This project is part of an application to the DoReMi internal call to consortium partners for integrated activities. The project addresses the collaborative projects accross WPs and the access to infrastructure part of the call. The project is a collabrat ion between three DoReMi consortium partners: UMB/CERAD (University of Life Sciences, Centre of Excellence in Environmental Radioactivity), Norwegian Institute of Public Health (NIPH) and Helmholz Zentrum München (HMGU, Germany). The proposal had been acc epted by the DoReMi consortium. The project application summary refers to UMBs contribution to the Ostanito project. As is known from radiotherapy patients, high-dose ionizing radiation in particular to children has the potential to increase the risk o f premature dementia or other neurodegenerative diseases (ND). The central hypothesis of the poroject is that low radiation doses to the brain, in particular early in life, may cause an accelerated development of ND conditions such as dementia or Parkinso n Disease (PD). A known risk-factor for ND is oxidative stress to the neuronal tissues, and this is known to be the preferential mode of damage at chronic low-dose rate ionising radiation. Groups of mice of wt, Pitx3EYL/EYL and Ogg1-/- genotypes and the combination of the latter two (compound homozygote Pitx3EYL/EYLOgg1-/-) will be subjected to the chronic gamma exposure either pre- and postnatally or postnatally only. The entire radiation exposure time will be 2 months with accumulated doses of 0 Gy (c ontrol), 0.1 Gy (LD) or 2 Gy (HD). UMB will have responsibility for the mice irradiation. the other partners (HMGU and NIPH), will be responsible for behavour and biological analysis. To make maximum usage of the FIGARO facility, we will also store oth er tissues relevant for non-cancer diseases (heart, muscle, liver, blood, eyes) in a central repository to be used by other DoReMi partners.