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Eriksson, Per
Publications (10 of 102) Show all publications
Buratovic, S., Stenerlöw, B., Sundell-Bergman, S., Fredriksson, A., Viberg, H., Gordh, T. & Eriksson, P. (2018). Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice. British Journal of Anaesthesia, 120(3), 546-554
Open this publication in new window or tab >>Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
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2018 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 120, no 3, p. 546-554Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
cognition, gamma rays, ketamine, mice, tau proteins
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-360552 (URN)10.1016/j.bja.2017.11.099 (DOI)000438191300019 ()29452811 (PubMedID)
Funder
Swedish Radiation Safety Authority
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Legrand, M., Elie, C., Stefani, J., Flores, N., Culeux, C., Delissen, O., . . . Dinocourt, C. (2016). Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure. Neurotoxicology, 52, 34-45
Open this publication in new window or tab >>Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure
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2016 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 52, p. 34-45Article in journal (Refereed) Published
Abstract [en]

The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40 mg/L and 120 mg/L and of GD18 fetuses exposed at 120 mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120 mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120 mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120 mg/L DU, but not at PNDO and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network.

Keywords
Neurogenesis, Heavy metal, Brain development, Telencephalon, Dentate gyrus
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-282040 (URN)10.1016/j.neuro.2015.10.007 (DOI)000370767500004 ()26506049 (PubMedID)
Available from: 2016-04-01 Created: 2016-04-01 Last updated: 2018-01-10Bibliographically approved
Buratovic, S., Stenerlöw, B., Fredriksson, A., Sundell-Bergman, S. & Eriksson, P. (2016). Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice. International Journal of Radiation Biology, 92(7), 371-379
Open this publication in new window or tab >>Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice
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2016 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 92, no 7, p. 371-379Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Low-dose radiation, nicotine, cholinergic system, cognition, brain development, behavior
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-282366 (URN)10.3109/09553002.2016.1164911 (DOI)000379933800003 ()27043364 (PubMedID)
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
Buratovic, S., Stenerlöw, B., Sundell-Bergman, S., Fredriksson, A., Viberg, H., Gordh, T. & Eriksson, P. (2016). Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse. Anesthesiology
Open this publication in new window or tab >>Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse
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2016 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed) Submitted
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-282371 (URN)
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
Eriksson, P., Buratovic, S., Fredriksson, A., Stenerlöw, B. & Sundell-Bergman, S. (2016). Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose-response effects and strain and sex comparison. Behavioural Brain Research, 304, 11-19
Open this publication in new window or tab >>Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose-response effects and strain and sex comparison
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2016 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 304, p. 11-19Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-282365 (URN)10.1016/j.bbr.2016.02.008 (DOI)000372939400002 ()26876140 (PubMedID)
Funder
Swedish Radiation Safety AuthorityEU, FP7, Seventh Framework Programme, 29552
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
Viberg, H., Hallgren, S., Hamberg, P. & Eriksson, P. (2016). Transcriptional alterations of cholinergic and dopaminergic genes in mice neonatally exposed to the combination of the pesticides carbaryl and chlorpyrifos. In: : . Paper presented at The 55th Annual Meeting of the Society of Toxicology,New Orleans, March 13–17, 2016. (pp. 329-329). , 150
Open this publication in new window or tab >>Transcriptional alterations of cholinergic and dopaminergic genes in mice neonatally exposed to the combination of the pesticides carbaryl and chlorpyrifos
2016 (English)Conference paper, Poster (with or without abstract) (Other academic)
Series
The Toxicologist: Supplement to Toxicological Sciences, ISSN 1096-6080 ; 150 (1)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289269 (URN)
Conference
The 55th Annual Meeting of the Society of Toxicology,New Orleans, March 13–17, 2016.
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2016-05-03Bibliographically approved
Lee, I., Eriksson, P., Fredriksson, A., Buratovic, S. & Viberg, H. (2015). Developmental neurotoxic effects of two pesticides: behavior and biomolecular studies on chlorpyrifos and carbaryl. Toxicology and Applied Pharmacology, 288(3), 429-438
Open this publication in new window or tab >>Developmental neurotoxic effects of two pesticides: behavior and biomolecular studies on chlorpyrifos and carbaryl
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2015 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 288, no 3, p. 429-438Article in journal (Refereed) Published
Abstract [en]

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5 mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0 mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8–12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

Keywords
Developmental neurotoxicology, Chlorpyrifos, Carbaryl, Acetylcholinesterase, Protein, Behavior
National Category
Other Biological Topics
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-261192 (URN)10.1016/j.taap.2015.08.014 (DOI)000363083600015 ()26314619 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 282957
Available from: 2015-09-03 Created: 2015-08-31 Last updated: 2017-12-04Bibliographically approved
Lee, I., Eriksson, P., Fredriksson, A., Buratovic, S. & Viberg, H. (2015). Developmental neurotoxic effects of two pesticides: behavior and neuroprotein studies on endosulfan and cypermethrin. Toxicology, 335, 1-10
Open this publication in new window or tab >>Developmental neurotoxic effects of two pesticides: behavior and neuroprotein studies on endosulfan and cypermethrin
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2015 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 335, p. 1-10Article in journal (Refereed) Published
Abstract [en]

Developmental neurotoxicity of industrial chemicals and pharmaceuticals have been of growing interest in recent years due to the increasing reports of neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and autism. Exposure to these substances during early development may lead to adverse behavior effects manifested at a later phase of life. Pesticides are a wide group of chemicals which are still actively used and residues are found in the environment and in food products.

The present study investigated the potential developmental neurotoxic effects of two different types of pesticides, endosulfan and cypermethrin, after a single neonatal exposure during a critical period of brain development. Ten-day-old male NMRI mice were administrated an oral dose of endosulfan or cypermethrin (0.1 or 0.5 mg/kg body weight, respectively). Levels of proteins were measured in the neonatal and adult brain, and adult behavioral testing was performed. The results indicate that both pesticides may induce altered levels of neuroproteins, important for normal brain development, and neurobehavioral abnormalities manifested as altered adult spontaneous behavior and ability to habituate to a novel home environment. The neurotoxic behavioral effects were also presentseveral months after the initial testing, indicating long-lasting or even persistent irreversible effects. Also, the present study suggests a possible link between the altered levels of neuroprotein and changes in behavior when exposed during a critical period of brain development.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-259789 (URN)10.1016/j.tox.2015.06.010 (DOI)000360517600001 ()26143737 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 282957
Available from: 2015-08-12 Created: 2015-08-12 Last updated: 2018-01-11Bibliographically approved
Buratovic, S., Stenerlöw, B., Fredriksson, A., Sundell-Bergman, S. & Eriksson, P. (2015). Low Dose Neonatal Co-exposure to Radiation and Ketamine Negatively Influences Cognition and Alters Neuroprotein Levels in theAdult Mouse. In: : . Paper presented at 15th International Congress of radiation Research, Kyoto, May 25-29, 2015.
Open this publication in new window or tab >>Low Dose Neonatal Co-exposure to Radiation and Ketamine Negatively Influences Cognition and Alters Neuroprotein Levels in theAdult Mouse
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2015 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289300 (URN)
Conference
15th International Congress of radiation Research, Kyoto, May 25-29, 2015
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2016-11-24Bibliographically approved
Eriksson, P., Buratovic, S., Stenerlöw, B., Fredriksson, A. & Sundell-Bergman, S. (2015). Low-dose Ionizing Radiation Interacts with Environmental Agents During Brain Development: Exacerbation of Cognitive Dysfunction inMice. In: : . Paper presented at 15th International Congress of Radiation Research, Kyoto, May 25-29, 2015.
Open this publication in new window or tab >>Low-dose Ionizing Radiation Interacts with Environmental Agents During Brain Development: Exacerbation of Cognitive Dysfunction inMice
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2015 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289297 (URN)
Conference
15th International Congress of Radiation Research, Kyoto, May 25-29, 2015
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2016-11-24Bibliographically approved
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