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Viberg, Henrik
Publications (10 of 74) 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
Philippot, G., Gordh, T., Fredriksson, A. & Viberg, H. (2017). Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period. Journal of Applied Toxicology, 37(10), 1174-1181
Open this publication in new window or tab >>Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period
2017 (English)In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 37, no 10, p. 1174-1181Article in journal (Refereed) Published
Abstract [en]

Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg – 1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice

Keywords
Paracetamol (acetaminophen), developmental neurotoxicity, neonatal mice, critical period, spontaneous behavior, habituation, cognitive impairments
National Category
Neurosciences Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-334493 (URN)10.1002/jat.3473 (DOI)000409913500005 ()28448685 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-01-13Bibliographically approved
Nyman, Y., Fredriksson, A., Lönnqvist, P.-A. & Viberg, H. (2016). Etomidate exposure in early infant mice (P10) does not induce apoptosis or affect behaviour. Acta Anaesthesiologica Scandinavica, 60(5), 588-596
Open this publication in new window or tab >>Etomidate exposure in early infant mice (P10) does not induce apoptosis or affect behaviour
2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 5, p. 588-596Article in journal (Refereed) Published
Abstract [en]

Background

Numerous animal studies have shown that all commonly used intravenous anaesthetic drugs and volatile agents may cause neuronal apoptosis following exposure in early life. Most studies have focussed on detecting increased apoptosis but their methods are not always readily transferrable to humans.

The lipid formulation of etomidate represents an alternative to the currently established intravenous anaesthetic agents but there is no animal or human data on apoptosis or long-term behavioural changes. The aim of our study was to investigate the effects of etomidate on cerebral neuronal apoptosis and long-term behavioural effects using an established mouse model that represents the clinically relevant period of anaesthesia during early infancy in humans.

Methods

Six groups of 10 day old mice (P10) were injected with either etomidate 0.3, 3 or 10 mg/kg, propofol 60 mg/kg, ketamine 50 mg/kg or placebo only. Apoptosis in the cerebral cortex and hippocampus was assessed 24 h after treatment (activated caspase-3). Late behavioural effects were tested at 2 months of age (spontaneous activity in a new environment).

Results

No evidence was found of differences in activated caspase 3-concentrations among the study groups. Significant late behavioural changes were only observed in the ketamine group.

Conclusion

A single dose of etomidate in early infant mice at P10 did not produce evidence of cerebral apoptosis or impaired adult motor behaviour.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289308 (URN)10.1111/aas.12685 (DOI)000373773700005 ()26763687 (PubMedID)
Available from: 2016-04-29 Created: 2016-04-29 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
Gaetan, P., Fredriksson, A. & Viberg, H. (2016). Neonatal exposure to acetamiophen (paracetamol) and CB1R agonist shos an additive adverese neurodevelopmental effects. In: : . Paper presented at The 55th Annual Meeting of the Society of Toxicology,New Orleans, March 13–17, 2016. (pp. 55-55). , 150
Open this publication in new window or tab >>Neonatal exposure to acetamiophen (paracetamol) and CB1R agonist shos an additive adverese neurodevelopmental effects
2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Series
The Toxicologist: Supplement to Toxicological Sciences, ISSN 1096-6080 ; 150 (1)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289271 (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
Hallgren, S. & Viberg, H. (2016). Postnatal exposure to PFOS, but not PBDE 99, disturb dopaminergic gene transcription in the mouse CNS. Environmental Toxicology and Pharmacology, 41, 121-126
Open this publication in new window or tab >>Postnatal exposure to PFOS, but not PBDE 99, disturb dopaminergic gene transcription in the mouse CNS
2016 (English)In: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 41, p. 121-126Article in journal (Refereed) Published
Abstract [en]

The CNS of breast feeding infants and toddlers may be exposed to persistent organic pollutants via lactational transfer. Here, 10 days old mice were exposed to single oral doses of either PFOS, PBDE99 or vehicle control and were examined for changes in dopaminergic gene transcription in CNS tissue collected at 24 h or 2 months post exposure.qPCR analyses of brain tissue from mice euthanized 24 h post exposure revealed that PFOS affected transcription of Dopamine receptor-D5 (DRD5) in cerebral cortex and Tyrosine hydroxylase (TH) in the hippocampus. At 2 months of age, mice neonatally exposed to PFOS displayed decreased transcription of Dopamine receptor-D2 (DRD2) and TH in hippocampus. No significant changes in any of the tested genes were observed in PBDE99 exposed mice. This indicates that PFOS, but not PBDE99, affects the developing cerebral dopaminergic system at gene transcriptional level in cortex and hippocampus, which may account for some of the mechanistic effects behind the aetiology of neuropsychiatric disorders.

Keywords
Perfluorinated chemical repellants; Brominated flame retardants; Developmental neurotoxicology; Dopaminergic system; Brain growth spurt
National Category
Ecology
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-267552 (URN)10.1016/j.etap.2015.11.016 (DOI)000370094500016 ()26686188 (PubMedID)
Available from: 2015-11-24 Created: 2015-11-24 Last updated: 2017-12-01Bibliographically approved
Gaetan, P., Nyberg, F., Gordh, T., Fredriksson, A. & Viberg, H. (2016). Short-term exposure and long-term consequences of neonatal exposure to Δ9-tetrahydrocannabinol (THC) and ibuprofen in mice. Behavioural Brain Research, 307, 137-144
Open this publication in new window or tab >>Short-term exposure and long-term consequences of neonatal exposure to Δ9-tetrahydrocannabinol (THC) and ibuprofen in mice
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2016 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 307, p. 137-144Article in journal (Refereed) Published
Abstract [sv]

Both Δ9-tetrahydrocannabinol (THC) and ibuprofen have analgesic properties by interacting with the cannabinoid receptor type 1 (CB1R) and the cyclooxygenase (COX) systems, respectively. Evaluation of these analgesics is important not only clinically, since they are commonly used during pregnancy and lactation, but also to compare them with acetaminophen, with a known interaction with both CB1R and the COX systems. Short-term exposure of neonatal rodents to acetaminophen during the first weeks of postnatal life, which is comparable with a period from the third trimester of pregnancy to the first years of postnatal life in humans, induces long-term behavioral disturbances. This period, called the brain growth spurt (BGS) and is characterized by series of rapid and fundamental changes and increased vulnerability, peaks around postnatal day (PND) 10 in mice. We therefore exposed male NMRI mice to either THC or ibuprofen on PND 10. At 2 months of age, the mice were subjected to a spontaneous behavior test, consisting of a 60 min recording of the variables locomotion, rearing and total activity. Mice exposed to THC, but not ibuprofen, exhibited altered adult spontaneous behavior and habituation capability in a dose-dependent manner. This highlights the potency of THC as a developmental neurotoxicant, since a single neonatal dose of THC was enough to affect adult cognitive function. The lack of effect from ibuprofen also indicates that the previously seen developmental neurotoxicity of acetaminophen is non-COX-mediated. These results might be of importance in future research as well as in the ongoing risk/benefit assessment of THC.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-289311 (URN)10.1016/j.bbr.2016.04.001 (DOI)000376549000016 ()27058925 (PubMedID)
External cooperation:
Available from: 2016-04-29 Created: 2016-04-29 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
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