| 1. |
- Alm, Henrik, et al.
(författare)
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Proteomic evaluation of neonatal exposure to 2,2,4,4,5-pentabromodiphenyl ether
- 2006
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 114:2, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to the brominated flame retardant 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) during the brain growth spurt disrupts normal brain development in mice and results in disturbed spontaneous behavior in adulthood. The neurodevelopmental toxicity of PBDE-99 has been reported to affect the cholinergic and catecholaminergic systems. In this study we use a proteomics approach to study the early effect of PBDE-99 in two distinct regions of the neonatal mouse brain, the striatum and the hippocampus. A single oral dose of PBDE-99 (12 mg/kg body weight) or vehicle was administered to male NMRI mice on neonatal day 10, and the striatum and the hippocampus were isolated. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we found 40 and 56 protein spots with significantly (p < 0.01) altered levels in the striatum and the hippocampus, respectively. We used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS) to determine the protein identity of 11 spots from the striatum and 10 from the hippocampus. We found that the levels of proteins involved in neurodegeneration and neuroplasticity (e.g., Gap-43/neuromodulin, stathmin) were typically altered in the striatum, and proteins involved in metabolism and energy production [e.g., alpha-enolase; gamma-enolase; ATP synthase, H+ transporting, mitochondrial F1 complex, beta subunit (Atp5b); and alpha-synuclein] were typically altered in the hippocampus. Interestingly, many of the identified proteins have been linked to protein kinase C signaling. In conclusion, we identify responses to early exposure to PBDE-99 that could contribute to persistent neurotoxic effects. This study also shows the usefulness of proteomics to identify potential biomarkers of developmental neurotoxicity of organohalogen compounds.
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| 2. |
- Almlöv, Cecilia, et al.
(författare)
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Sweden
- 2024. - 1
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Ingår i: Global Perspectives on Enhancing Doctoral Co-Supervision. - Singapore : Springer Publishing Company. - 9789819704620 - 9789819704606 ; , s. 113-125
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Bokkapitel (refereegranskat)abstract
- Swedish law requires all doctoral students to be co-supervised. Individualsseeking to become primary supervisors are required to complete doctoral supervisiontraining programs to ensure they are equipped with necessary competencies to guidedoctoral students. This chapter uses interviews, surveys, and documents to explore cosupervision and the experiences of co-supervisors, providing insights and comparingto global practices. We provide a historical overview of co-supervison in Sweden,covering its development over the past 70 years. We then analyse different types ofsupervision in terms of involvement and formality. Next then describe the contextualsetting by examining supervision guidelines, supervisors’ role expectations, and workallocation. We then explore the definition, application, experience, and regulationof co-supervison in Sweden. Drawing from this analysis, we showcase successfulinstances of co-supervison in Sweden and address the associated challenges. Thischapter offers a thorough examination of co-supervision practices, encompassingtheir historical origins, present implementation, and prospective advancements.
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| 3. |
- Buratovic, Sonja, et al.
(författare)
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Comparison of single and repeated exposure to low doses of pyrethroids, permethrin and bioallethrin, during neonatal brain development on adult spontaneous behaviour
- 2012
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Konferensbidrag (refereegranskat)abstract
- Permethrin and bioallethrin belong to the Type 1 class of pyrethroid pesticides. The primary mechanism of action is interference with nerve membrane sodium channels that results in increased neuronal activity. We have earlier reported on developmental neurotoxic effects after repeated, PND 10 to PND16, neonatal exposure to pyrethroids. The effects were manifested as altered spontaneous behavior, hyperactivity and reduced cognitive function and changes in cholinergic muscarinic/nicotinic receptors in the cerebral cortex of neonatal and adult mice. The present study was undertaken to compare repeated and single exposure to permethrin and bioallethrin during the neonatal brain growth spurt (BGS) on adult spontaneous behavior in a novel home environment. Neonatal NMRI male mice were given permethrin, orally (0.55; 3.3; 6.6 mg/kg bw/day) on PND 10-14, or just a single oral dose of 6.6 mg/kg bw on PND 10. Bioallethrin was given as a single oral dose of 0.7 mg/kg bw on PND 10, and compared to earlier published data on repeated exposure. Mice serving as controls received the 20 % fat emulsion vehicle. Spontaneous behavior test (locomotion, rearing, total activity) in 2-month-old mice revealed a significant higher activity in mice exposed to repeated doses of 6.6 mg permethrin, as well in mice just receiving a single 6.6 mg dose of permethrin. No significant difference was observed between repeated and single exposure. A single dose of 0.7 mg bioallethrin on PND 10 caused the same effects as a repeated dose of 0.7 mg between PND 10 to PND 16. This demonstrates that a single dose of these pyrethroids can cause the same developmental neurotoxic effects as that seen following repeated doses over one week during the neonatal BGS period in mouse. This research provides is consistent with previous findings that exposure during the BGS can result in persistent behavioral defects.
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| 4. |
- Buratovic, Sonja, et al.
(författare)
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Developmental exposure to PBDE 209 : sex, neuroprotein and neurobehavioural analyses
- 2012
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Ingår i: Toxicology Letters. - 0378-4274 .- 1879-3169. ; 211:supplement, s. S90-
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardants in polymers products.Newborns and toddlers can be indirectly and directly exposed to PBDEs during a period of critical rapid brain development. The present study was undertaken to investigate neurotoxic effects after neonatal exposure to PBDE 209 on sex differences, cognitive function, neuroproteins and altered susceptibility to toxicants in adults. 3-day-old NMRI mice were exposed to PBDE 209 (2,2´,3,3´,4,4´,5,5´,6,6´-decaBDE at 0, 1.4, 6.0 and 14 µmol/kg bw). At 2 months of age male mice were exposed to paraoxon (0.25 mg/kg bw, every 2nd day for 7 days) and female mice exposed to nicotine (80 µg nicotine base/kg bw). At the age of 2 and 4 months mice were observed for spontaneous behaviour, before and after adult exposure to paraoxon (male) and nicotine (female). Male mice aged 5 and 7 months were observed for memory and learning. Neuroproteins CaMKII, GAP-43, synaptophysin and tau in cerebral cortex and hippocampus from 7-months old male and female mice were analyzed. The present study shows that neonatal exposure to PBDE 209 can induce developmental neurobehavioural defects in both male and female mice. Neonatal exposure to PBDE 209 also caused increased susceptibility in adult mice to paraoxon and nicotine. All these effects were dose response related. Further, neonatal exposure to PBDE 209 caused persistent defects in memory and learning in adult male mice and increased levels of important neuroproteins e.g. tau in adult male and female mice.
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| 5. |
- Buratovic, Sonja, et al.
(författare)
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Developmental exposure to PBDE 209 alters adult susceptibility to paraoxon and nicotine : gender and neurobehavioural analysis
- 2011
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Konferensbidrag (refereegranskat)abstract
- Newborns, infants and children can be indirectly and directly exposed to PBDEs. This exposure coincides with a period of rapid brain development. Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardants in polymers, especially in electric appliances.A concern is that these compounds are present at a higher level in newborns and toddlers than in the average adult individual, especially the highly brominated PBDEs. We have earlier reported that neonatal exposure to toxicants can lead to an increased susceptibility of the cholinergic system at adult age. The present study was undertaken to investigate whether neonatal exposure of male and female mice to PBDE 209 alters the adult susceptibility to the organophosphorous compound, paraoxon, and to nicotine, respectively.. Neonatal, 3-day-old, NMRI mice were exposed to PBDE 209 (2,2´,3,3´,4,4´,5,5´,6,6´-decaBDE at 1.4, 6.0 and 14 µmol/kg bw). At two months of age male mice were exposed to paraoxon (0.25 mg/kg bw, every 2nd day for 7 days) and female mice exposed to nicotine. At the age of 2 months male and female mice were observed for spontaneous behaviour in a novel home environment, before and after adult exposure to paraoxon and nicotine, respectively. Adult male and female mice neonatally exposed to PBDE 209 showed significant impaired spontaneous behaviour. Male mice neonatally exposed to PBDE 209 and to paraoxon as adults developed additional defect spontaneous behaviour and lack of habituation. Female mice neonatally exposed to PBDE 209 showed an increased susceptibility to nicotine, where PBDE 209 exposed mice responded with a decrease in activity to nicotine whereas control mice responded with increased activity. The present study shows that PBDE 209 can induce developmental neurobehavioural defects in both male and female mice. Neonatal exposure to PBDE 209 caused also increased susceptibility in adult mice to paraoxon and nicotine. All these effects were dose response related.
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| 6. |
- Buratovic, Sonja, et al.
(författare)
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Developmental exposure to the polybrominated diphenyl ether PBDE 209 : Neurobehavioural and neuroprotein analysis in adult male and female mice
- 2014
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Ingår i: Environmental Toxicology and Pharmacology. - : Elsevier BV. - 1382-6689 .- 1872-7077. ; 38:2, s. 570-585
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs), used as flame retardants in polymer products, are reported to cause developmental neurotoxic effects in mammals. The present study have investigated neurotoxic effects arising from neonatal exposure to PBDE 209, including alterations in sex differences, spontaneous behaviour, learning and memory, neuroproteins and altered susceptibility of the cholinergic system in adults. Three-day-old NMRI mice, of both sexes, were exposed to PBDE 209 (2,2',3,3',4,4',5,5',6,6'-decaBDE at 0, 1.4, 6.0 and 14.0 mu mol/kg b.w.). At adult age (2-7 months) a similar developmental neurotoxic effects in both male and female mice were seen, including lack of or reduced habituation to a novel home environment, learning and memory defects, modified response to the cholinergic agent's paraoxon (males) and nicotine (females) indicating increased susceptibility of the cholinergic system. The behavioural defects were dose-response related and persistent. In mice of both sexes and showing behavioural defects, neuroprotein tau was increased. (C) 2014 Elsevier B.V. All rights reserved.
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| 7. |
- Buratovic, Sonja, 1986-, et al.
(författare)
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Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
- 2018
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 120:3, s. 546-554
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.
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| 8. |
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| 9. |
- Buratovic, Sonja, 1986-
(författare)
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Low-Dose Ionizing Radiation Induces Neurotoxicity in the Neonate : Acute or fractionated doses and interaction with xenobiotics in mice
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the developmental neurotoxic effects of exposure to low-dose ionizing radiation (IR), alone or together with xenobiotics, during a critical period of neonatal brain development in mice.During mammalian brain development there is a period called the brain growth spurt (BGS), which involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to xenobiotics can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. In humans, the BGS starts during the third trimester of pregnancy and continues for approximately 2 years in the child. The present thesis has identified a defined critical period, during the BGS, when IR can induce developmental neurotoxicity in mice. The observed neurotoxicity was not dependent on sex or strain and manifested as altered neurobehaviour in the adult mouse. Furthermore, fractionated dose exposures appear to be as potent as a higher acute dose. The cholinergic system can be a target system for developmental neurotoxicity of IR, since alterations in adult mouse cholinergic system susceptibility were observed. Co-exposure to IR and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction. Furthermore, co-exposure with the environmental agent paraquat has indicated that the dopaminergic system can be a potential target. In this thesis, clinically relevant doses of IR and a sedative/anesthetic agent (ketamine) were shown to interact and exacerbate defects in adult mouse neurobehaviour, learning and memory, following neonatal exposure, at doses where the single agents did not have any impact on the measured variables. This indicates a shift in the dose-response curve for IR, towards lower doses, if exposure occurs during the neonatal brain development. In addition, co-exposed mice, showing cognitive defects, expressed elevated levels of tau protein in the cerebral cortex. Furthermore, exacerbation of neurochemical deviations were observed following co-exposure compared to irradiation alone.Further investigations of neurotoxic effects following fractionated or acute low-dose IR, modelling the clinical situation during repeated CT scans or levels of radiation deposited in non-target tissue during radiotherapy, and possible interaction effects with xenobiotics, is of great importance in the field of radioprotection.
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| 10. |
- 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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