Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult mice.

Radiological methods for screening, diagnostics and therapy are often used in healthcare; however, it has recently been reported that developmental exposure to low-dose ionizing radiation (IR) causes neurotoxicity. Environmental chemicals also have the potential to affect the developing brain and the concomitant effects caused by IR and chemicals are of high interest today. We therefore aim to investigate if low-dose IR can interact with the known neurotoxicant paraquat to induce neurotoxicity in the neonatal mouse model. Using the same model, we also aim to investigate if fractionated low-dose IR can be as neurotoxic as higher acute doses. Male mice were exposed to a single dose of paraquat (0.2 or 0.02 mg/kg) on postnatal day 10 and 11. Two hours following paraquat exposure, mice were whole body irradiated with 100 or 300 mGy gamma radiation (137 Cs). Behavioural observations were performed at 2 and 3 months of age. Following behavioural testing, we evaluated striatal dopaminergic gene transcription. Animals co-exposed to IR and paraquat generally displayed altered spontaneous behaviour compared to controls and single agent exposed mice. Stronger effects by combined exposure were also observed on adult memory and learning. However, dopaminergic gene transcript levels remained unchanged by treatment. Co-exposure to low-dose IR and paraquat can interact to exacerbate neurotoxic effects and to impair cognitive function. Furthermore, fractionation of the radiation dose was observed to be as potent as higher acute exposure for induction of developmental neurotoxicity.

Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice.

PURPOSE: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice. MATERIALS AND METHODS: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 µg/kg b.w.) twice daily on postnatal day (PND) 10, 10-11, 10-12 or 10-13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior. RESULTS: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine. CONCLUSIONS: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose--response effects and strain and sex comparison.

Development of the brain includes periods which can be critical for its normal maturation. The present study investigates specifically vulnerable peri-/postnatal periods in mice which are essential for understanding the etiology behind radiation induced neurotoxicity and functional defects, including evaluation of neurotoxicity between sexes or commonly used laboratory mouse strains following low/moderate doses of ionizing radiation (IR). Male Naval Medical Research Institute (NMRI) mice, whole body irradiated to a single 500 mGy IR dose, on postnatal day (PND) 3 or PND 10 showed an altered adult spontaneous behaviour and impaired habituation capacity, whereas irradiation on PND 19 did not have any impact on the studied variables. Both NMRI and C57bl/6 male and female mice showed an altered adult spontaneous behaviour and impaired habituation following a single whole body irradiation of 500 or 1000 mGy, but not after 20 or 100 mGy, on PND 10. The present study shows that exposure to low/moderate doses of IR during critical life stages might be involved in the induction of neurological/neurodegenerative disorder/disease. A specifically vulnerable period for radiation induced neurotoxicity seems to be around PND 3-10 in mice. Further studies are needed to investigate mechanisms involved in induction of developmental neurotoxicity following low-dose irradiation.

Modelling (137)Cs concentrations in moose (1986-2012) from areas highly contaminated by the Chernobyl fallout.

Data from long term annual monitoring of (137)Cs concentrations in harvested moose (Alces alces) were empirically modelled by applying multivariate data analysis that is able to from relatively raw datasets show how the many various impact variables are related (Principal component analysis, PCA). In the later stage regression modelling (Partial least squares, PLS) was applied to analyse which environmental and physiological factors were significant (i.e. of predictive value) based on the measured (X) activity concentrations in moose meat. The data sets originate from two different forest dominated areas in Sweden. One area is located inland (Heby municipality) and the other borders to the Baltic Sea (Gävle municipality). In inland with 20% farmland, GIS-software was used to calculate the proportion of different habitat types and (137)Cs deposition around individual killing spots. This model reveals that the proportions of farmland and forest around the killing spot were significant parameters, second to deposition and years since fallout. Significance was also obtained for the proportions of mire and water bodies, the amount of rain in summer and the age of the moose. In the other model based on data from the coastal area with only about 4% farmland, the coordinates of the moose killing spots were not recorded in the data sets. In the resulting model the temperature in July was the most important parameter, second to years since fallout. Significance was also found for the following parameters: temperature and rainfall in several summer months, the approximate north- and eastward location of the killing spot and to which age category (adult/calf) the harvested moose belonged.

Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice.

Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.

Interaction of gamma-radiation and methyl mercury during a critical phase of neonatal brain development in mice exacerbates developmental neurobehavioural effects.

In our environment, mammals (including humans) are exposed to various types of ionizing radiation and both persistent and non-persistent toxic chemicals. It is known that ionizing radiation, as well as methyl mercury, can induce neurotoxicological and neurobehavioural effects in mammals. These developmental neurotoxic effects can be seen following exposure during gestation. There is a lack of knowledge concerning the effects and consequences of low-dose exposure during critical phases of perinatal and/or neonatal brain development, and of the combination of ionizing radiation and environmental chemicals. A recent study has indicated that low doses of ionizing radiation to the human brain during infancy influence cognitive ability in adulthood. In the present study, 10-day old neonatal male NMRI mice were exposed to a single oral dose of MeHg (0.40 or 4.0 mg/kg bw). Four hours after the MeHg exposure the mice were subjected to (60)Co gamma-radiation on one occasion at doses of 0.2 and 0.5 Gy. The animals were then subjected to a spontaneous behaviour test at 2 and 4 months, and a water maze test at the age of 5 months. Neither the single dose of MeHg (0.4 mg/kg bw) nor the radiation dose of 0.2 Gy affected their spontaneous behaviour, whereas the co-exposure to external gamma-radiation and MeHg caused developmental neurotoxic effects. The study shows that gamma-radiation and MeHg can interact and significantly exacerbate developmental neurotoxic effects, as manifested by disrupted spontaneous behaviour, lack of habituation, and impaired learning and memory functions.

Assessing ecological effects of radionuclides: data gaps and extrapolation issues.

By inspection of the FASSET database on radiation effects on non-human biota, one of the major difficulties in the implementation of ecological risk assessments for radioactive pollutants is found to be the lack of data for chronic low-level exposure. A critical review is provided of a number of extrapolation issues that arise in undertaking an ecological risk assessment: acute versus chronic exposure regime; radiation quality including relative biological effectiveness and radiation weighting factors; biological effects from an individual to a population level, including radiosensitivity and lifestyle variations throughout the life cycle; single radionuclide versus multi-contaminants. The specificities of the environmental situations of interest (mainly chronic low-level exposure regimes) emphasise the importance of reproductive parameters governing the demography of the population within a given ecosystem and, as a consequence, the structure and functioning of that ecosystem. As an operational conclusion to keep in mind for any site-specific risk assessment, the present state-of-the-art on extrapolation issues allows us to grade the magnitude of the uncertainties as follows: one species to another > acute to chronic = external to internal = mixture of stressors > individual to population > ecosystem structure to function.

Radiological protection of the environment from the Swedish point of view.

The current system of radiological protection is aimed at protecting human health, and largely neglects both the effects of radiation on the environment and the managerial aspects of environmental protection. The Swedish Radiation Protection Act was revised in 1988 and includes environmental protection as one of its aims. In practice, little guidance had been given in the regulations based on the Act until 1998, when the Swedish Radiation Protection Authority (SSI) formulated environmental aims in its regulations concerning protection of human health and the environment in connection to the final management of spent nuclear fuel and waste. These regulations focus on protection of biodiversity and biological resources, based on ecosystem characterisation. In a broader perspective, the Swedish Parliament established 15 national environmental quality objectives in 1999, covering all aspects of protecting the environment, including the effects of radiation. This paper reviews the background for radiological protection of the environment from both an international and a Swedish perspective, describing the aims and current activities in establishing a system for assessing environmental effects and their consequences that can be used in decision-making. Such activities are largely a result of the European Union research project FASSET (Framework for Assessment of Environmental Impact), carried out under the 5th Framework Programme of the Union. This work is complemented at the Swedish national level by government support to initiate a national environmental monitoring and assessment programme for characterising the radiation environment, which will provide the foundation for decision-making.