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- Bajinskis, Ainars, 1973-
(författare)
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Studies of DNA repair strategies in response to complex DNA damages
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this thesis was to study the role of the indirect actions of γ-rays and α-particles on the complexity of primary DNA damages and the repair fidelity of major DNA repair pathways: non-homologous end joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER). The complexity of radiation-induced damages increases and the proximity between damages decreases with increasing LET due to formation of ionization clusters along the particle track. The complexity of damages formed can be modified by the free radical scavenger dimethyl sulfoxide (DMSO). In addition, the effects of low doses of low dose rate γ-radiation on cellular response in terms of differentiation were investigated.Paper I investigates the role of the indirect effect of radiation on repair fidelity of HRR, NHEJ and BER when damages of different complexity were induced by radiation or by potassium bromate. We found that potassium bromate induces complex DNA damages through processing of base modifications and that the indirect effect of radiation has a high impact on the NHEJ pathway. Results in paper II confirmed our conclusions in paper I that the indirect effect from both γ-rays and α-particles has an impact on all three repair pathways studied and NHEJ benefits the most when the indirect effect of radiation is removed.In paper III we investigated the effects of low dose/dose rate γ-radiation on the developmental process of neural cells by using cell models for neurons and astrocytes. Our results suggest that low dose/dose rate γ-radiation attenuates differentiation and down-regulates proteins involved in the differentiation process of neural cells by an epigenetic rather than cytotoxic mechanism.
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| 4. |
- Buratovic, Sonja, et al.
(författare)
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Exposure to a single dose of ionising radiation during brain development can cause cognitive defects and increased levels of tau in mice
- 2012
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Konferensbidrag (refereegranskat)abstract
- Ionising radiation (IR) is widely used in the medical field for treating tumours, including tumours in the central nervous system, and for imaging techniques such as computed tomography (CT). There is a lack of knowledge and increasing concern about effects and consequences from low dose exposure during critical phases of perinatal and/or neonatal brain development compared to prenatal irradiation. It is known that IR causes neurotoxicological and neurobehavioural defects in mammals. Further, an epidemiological study has suggested that low doses of IR to the human brain during infancy can have a negative effect on cognitive abilities in adulthood. The rapid brain growth spurt (BGS) occurs in humans as well as mice. In humans the BGS starts during the third trimester of pregnancy and continues throughout the first two years of life. In mouse and rat the BGS is neonatal, spanning the first 3-4 weeks of life. The BGS is characterized by maturation of axonal and dendritic outgrowth, establishment of neural connections and acquisition of many new motor and sensory abilities. By using the neonatal mouse as an animal model we are able to study the effect of IR during early periods of brain development and which consequences it has for the adult animal. Disturbances in development caused by nicotine, MeHg, PCBs and PBDEs have previously been shown to alter adult spontaneous behaviour and/or neuroprotein levels in mice.Neonatal NMRI male mice were irradiated (0; 0.35 and 0.5 Gy) at one single occasion on postnatal day 10. Mice serving as controls were placed in plastic dishes for a time-period corresponding to the irradiation. Spontaneous behaviour was tested in a novel home environment at 2- and 4-months of age and parameters observed were locomotion, rearing and total activity. Analyses of important neuroprotein levels were performed on 6-month-old control and 0.5 Gy irradiated mice.Spontaneous behaviour test (locomotion, rearing, total activity revealed a significantly deranged behaviour in 2- and 4-month old mice irradiated with 0.35 or 0.5 Gy in a dose-response related manner, when compared to controls. The behavioural alterations were manifested as a reduced activity during at the beginning of the observational period and a higher activity at the end of the observational period. Analyses of the neuroprotein tau, which in human medicine is used as a biomarker for Alzheimer’s disease, showed a significantly higher level in mice irradiated with 0.5 Gy compared to controls. This demonstrates that a single dose of gamma radiation, given at a defined critical time period during brain development, is sufficient to cause persistently reduced cognitive functions and increased levels of tau in mice.
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| 5. |
- Buratovic, Sonja, et al.
(författare)
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Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
- 2014
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 45, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, butprocedures 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 toIR 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 gammaradiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of bothsexes were observed for spontaneous behaviour in a novel home environment. The neuroproteinsCaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus wereanalysed 24 h 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 micewas observed, where both males and females displayed a modified habituation, indicating reducedcognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male miceshowed 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 criticalperiod of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, anelevation of tau protein was observed in male mice displaying reduced cognitive function.
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| 6. |
- Buratovic, Sonja, et al.
(författare)
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Neonatal exposure to a single low dose of ionising radiation causes persistent disruptions in cognitive abilities and increased levels of tau in mice
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Ionising radiation (IR) is extensively used in the medical field for treatment and diagnostics. Concern has been raised about possible negative consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. The brain growth spurt, which is characterized by maturation of axonal and dendritic outgrowth, establishment of neural connections and acquisition of new motor and sensory abilities, occurs perinatally in humans and neonatally in mice. By using the neonatal mouse as an animal model we are able to study the effect of IR during early periods of brain development and which consequences it has for the adult animal.Neonatal NMRI mice were irradiated (0; 0.35 and 0.5 Gy) at one single occasion on postnatal day 10. At 2- and 4-months of age, spontaneous behaviour was tested in a novel home environment and parameters observed were locomotion, rearing and total activity. Analyses of important neuroproteins in cerebral cortex were performed 24h following irradiation (0 and 0.5 Gy) and at 6-months of age.Observations of spontaneous behaviour revealed a significantly deranged behaviour in 2- and 4-month old mice of both sexes irradiated with 0.35 or 0.5 Gy in a dose response related manner. The observed reduced activity during the beginning of the test period and increased activity at the end of the test period indicates a lack of habituation capacity and disrupted cognitive functions. Neuroprotein analyses of cerebral cortex 24h after irradiation and at 6-months of age showed a significantly increased level of tau in mice irradiated with 0.5 Gy compared to controls. This demonstrates that a single dose of IR, given at a defined critical period during brain development, is sufficient to cause persistently reduced cognitive functions and increased levels of tau in mice.
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| 9. |
- Eriksson, Per, et al.
(författare)
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Interaction of gamma-radiation and methyl mercury during a critical phase of neonatal brain development in mice exacerbates developmental neurobehavioral effects
- 2010
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 31:2, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- 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 pen natal 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 Co-60 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.
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