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Fredriksson, Anders
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Publications (10 of 117) Show all publications
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
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
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
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
Färdig, R., Fredriksson, A., Lewander, T., Melin, L. & Mueser, K. (2016). Neurocognitive functioning and outcome of the Illness Management and Recovery Program for clients with schizophrenia and schizoaffective disorder. Nordic Journal of Psychiatry, 70(6), 430-435
Open this publication in new window or tab >>Neurocognitive functioning and outcome of the Illness Management and Recovery Program for clients with schizophrenia and schizoaffective disorder
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2016 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 6, p. 430-435Article in journal (Refereed) Published
Abstract [en]

The relationship between psychosocial programming and neurocognition has been established in previous research, but has not been explored in the context of the Illness Management and Recovery Program (IMR). This study examined associations between neurocognition and illness self-management skills acquisition, based on two previous trials of IMR. Neurocognitive functioning was assessed at baseline and post-treatment in 53 participants with schizophrenia or schizoaffective disorder who completed the IMR. Illness self-management was measured by the client and clinician versions of the Illness Management and Recovery Scale. Statistical analyses investigated improvements in neurocognitive functioning and possible association between illness self-management skills acquisition and neurocognitive functioning. Speed of processing as measured by the Trail Making Test A, was related to client-reported acquisition of illness self-management skills, before and after controlling for psychiatric symptoms and medication, but did not predict improvement in clinician ratings of client illness self-management skills. However, when controlling for client session attendance rates, the association between speed of processing and client-reported illness self-management skills acquisition ceased to be statistically significant, which suggests that compromised neurocognitive functioning does not reduce response to training in illness self-management in itself. The association between the frequency of attended IMR sessions and outcome of the IMR seems to decrease the negative impact of compromised neurocognition on illness self-management skills acquisition. Also, clients with slower speed of processing may experience less benefit from the IMR and may attend fewer sessions.

Keywords
Illness management; neurocognition; recovery; schizophrenia
National Category
Psychiatry
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-175236 (URN)10.3109/08039488.2016.1146797 (DOI)000379532900006 ()26936087 (PubMedID)
Available from: 2012-06-04 Created: 2012-06-04 Last updated: 2017-12-07Bibliographically 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
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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