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  • 251.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Exposure to polybrominated diphenyl ethers 203 and 206 during the neonatal brain growth spurt affects proteins important for normal neurodevelopment in mice2009In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 109, no 2, p. 306-311Article in journal (Refereed)
    Abstract [en]

    The period of rapid brain growth and development (BGS) is postnatal in mice and rats, spanning the first 3-4 weeks of life, reaching its peak around postnatal day 10, whereas in humans, the BGS is perinatal. CaMKII, GAP-43, synaptophysin, and tau play important roles during the BGS. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), is present and increasing in the environment and in human milk. The only congener still in use, decabrominated diphenyl ether (PBDE 209), is thought to be debrominated into lower brominated congeners. In the present study, nona- and octabrominated PBDEs were examined. Neonatal mice were exposed to 21 mumol PBDE 203 or 206/kg bodyweight on postnatal day 10, and different brain regions were analyzed for CaMKII, GAP-43, synaptophysin, and tau, 24 h after exposure. The protein analysis showed that CaMKII and synaptophysin increased significantly in the hippocampus, but not in the cerebral cortex, after neonatal exposure to PBDE 203 or 206. Furthermore, there were no significant changes in the levels of GAP-43 and tau in the cerebral cortex or hippocampus after neonatal exposure to PBDE 203 or 206. This shows that PBDE 203 and 206 affect important proteins involved in normal maturation of the brain and strengthens our findings that highly brominated PBDEs cause developmental neurotoxicity. In addition, the increases in CaMKII and synaptophysin are the same changes seen after neonatal PBDE 209 exposure; supporting the suggestion that PBDE 209 must be metabolized, likely debrominated into lower brominated PBDEs, to exert its neurotoxic effects.

  • 252.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal Developmental Neurotoxicity of Brominated Flame Retardants, the Polybrominated Diphenyl Ethers (PBDEs)2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines developmental neurotoxic effects of polybrominated diphenyl ethers (PBDEs), PBDE 99, PBDE 153, and the fully brominated PBDE 209, after exposure during the newborn period in rodents.

    Our environment contains vast numbers of contaminants, including the flame retardants, PBDEs. The PBDEs are widely found in the environment and are increasing in human milk. Individuals can be exposed to PBDEs during their whole lifetime, and especially during the lactation period. The neonatal period, coinciding with the lactation period, is characterized in many mammalian species by rapid growth and development of the immature brain. It has been shown that numerous toxicants can induce permanent disorders in brain function when administered to the neonatal mouse during the brain growth spurt (BGS). In mice and rats this period is postnatal, spanning over the first 3-4 weeks of life, while in humans, BGS begins during the third trimester of pregnancy and continues throughout the first two years of life.

    The present studies identified a defined critical period during BGS in mice when the brain is vulnerable to insults of low doses of PBDEs and that it is the presence of PBDEs or their metabolites in the brain during this critical period that is crucial to evoking neurotoxic effects. The effects observed are permanent altered spontaneous behavior, reduced habituation, deficits in learning and memory, and disturbances in the cholinergic system. These effects worsen with age.

    The ability of PBDEs to induce neurotoxic effects does not appear to be gender-, strain- or species-specific, because the neurotoxic effects are induced in rats and male and female mice of different strains.

    The developmental neurotoxic effects of PBDEs are similar to those observed for polychlorinated biphenyls (PCBs) and possible interactive effects of PBDEs and other environmental contaminants are therefore of concern.

    List of papers
    1. A brominated flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether: Uptake, retention and induction of neurobehavioural derangement in mice, during a critical phase of neonatal brain development.
    Open this publication in new window or tab >>A brominated flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether: Uptake, retention and induction of neurobehavioural derangement in mice, during a critical phase of neonatal brain development.
    Show others...
    2002 In: Toxicological Sciences, Vol. 67, p. 98-103Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92200 (URN)
    Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
    2. Neonatal exposure to 2,2´,4,4´,5-pentabromodiphenyl ether causes increased susceptibility in the cholinergic transmitter system at adult age.
    Open this publication in new window or tab >>Neonatal exposure to 2,2´,4,4´,5-pentabromodiphenyl ether causes increased susceptibility in the cholinergic transmitter system at adult age.
    2002 In: Toxicological Sciences, Vol. 67, p. 104-107Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92201 (URN)
    Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
    3. Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory and decreases hippocampal cholinergic receptors in adult mice.
    Open this publication in new window or tab >>Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory and decreases hippocampal cholinergic receptors in adult mice.
    2003 In: Toxicology and Applied Pharmacology, Vol. 192, p. 95-106Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92202 (URN)
    Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
    4. Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development.
    Open this publication in new window or tab >>Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development.
    Show others...
    2003 In: Toxicological Sciences, Vol. 76, p. 112-120Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92203 (URN)
    Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
    5. Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice
    Open this publication in new window or tab >>Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice
    2004 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 81, no 2, p. 344-353Article in journal (Refereed) Published
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), one class of flame retardants used to suppress or inhibit the risk of fire, are regularly found in the environment and in human milk. The present study shows that neonatal exposure to a widely, environmentally found PBDE, 2,2',4,4',5-pentaBDE (PBDE 99), can induce developmental neurotoxic effects, such as changes in spontaneous behavior (hyperactivity), effects that are dose-response related and worsen with age. These changes are seen in C57/Bl mice of both sexes. Neonatal C57/Bl male and female mice were orally exposed on day 10 to 0.4, 0.8, 4.0, 8.0, or 16 mg PBDE 99/kg body weight. Spontaneous behavior (locomotion, rearing, and total activity) was observed in two-, five-, and eight-month-old mice. The behavior tests showed that the effects were dose-response and time-response related for both male and female mice. The observed developmental neurotoxic effects seen for PBDE 99, in C57/Bl mice, are similar to effects seen for 2,2',4,4'-tetraBDE (PBDE 47), PBDE 99, 2,2',4,4',5,5'- hexaBDE (PBDE 153), 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) and for certain PCBs, in male NMRI mice. Furthermore, the effects of PBDEs appear to be as potent in female mice as in male mice, and as potent in C57/Bl mice as in NMRI mice, concerning developmental neurotoxicity.

    Keywords
    spontaneous behavior, neonatal, flame retardants, polybrominated diphenyl ethers, gender comparison
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-92204 (URN)10.1093/toxsci/kfh215 (DOI)
    Available from: 2004-10-06 Created: 2004-10-06 Last updated: 2017-12-14Bibliographically approved
    6. Deranged spontaneous behaviour and decrease in cholinergic muscarinic receptors in hippocampus in the adult rat, after neonatal exposure to the flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99).
    Open this publication in new window or tab >>Deranged spontaneous behaviour and decrease in cholinergic muscarinic receptors in hippocampus in the adult rat, after neonatal exposure to the flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99).
    Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-92205 (URN)
    Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
  • 253.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal ontogeny and neurotoxic effect of decabrominated diphenyl ether (PBDE 209) on levels of synaptophysin and tau2009In: International Journal of Developmental Neuroscience, ISSN 0736-5748, E-ISSN 1873-474X, Vol. 27, no 5, p. 423-429Article in journal (Refereed)
    Abstract [en]

    Mice and rats have a period of rapid growth and development that occurs postnatally, while in humans the corresponding period is perinatal. This gives us the opportunity to study direct effects of chemicals during developmental processes of the central nervous system (CNS) in murine animals. Mammals have a marked period of rapid brain growth and development, the brain growth spurt (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. The proteins synaptophysin and tau are involved in developmental processes in the nervous system during the BGS in mice. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), is present and increasing in the environment and in human milk, which is also true for the only congener still in use, decabrominated diphenyl ether (2,2',3,3',4,4',5,5',6,6'-decaBDE, PBDE 209). The present study was divided into two parts (a) the neonatal ontogeny of synaptophysin and tau and (b) the developmental neurotoxic effect of PBDE 209 on synaptophysin and tau during the neonatal ontogeny in mice. The level of synaptophysin measured on postnatal days 1, 3, 7, 10, 14, and 28, increased continuously during the neonatal period, while tau has a bell-shaped ontogeny curve that peaks between postnatal days 7 and 10. The effects of PBDE 209 on the developmental expression of synaptophysin and tau were examined in neonatal NMRI male mice, orally exposed on day 3 to 20.1mg PBDE 209/kg body weight. The animals were euthanized 7 days after exposure to PBDE 209 and levels of synaptophysin and tau were analyzed in the hippocampus and cerebral cortex. The protein analysis showed that synaptophysin had increased significantly in the hippocampus, but not in the cerebral cortex, in mice 7 days after exposure to PBDE 209. The analysis of protein levels showed no changes in tau in the hippocampus or cerebral cortex 7 days after exposure to PBDE 209 on postnatal day 3. A recent study shows that neonatal PBDE 209-exposure can affect levels of BDNF (brain-derived neurotrophic factor), CaMKII (Ca(2+)/calmodulin-dependent protein kinase II), and GAP-43 (growth associated protein 43), which are proteins that are important for normal brain development. The present study shows that PBDE 209 affects the level of synaptophysin in the developing brain, which further supports the recent findings that PBDE 209 can disturb components of normal brain maturation and act as a developmental neurotoxicological agent. Furthermore, this suggests that certain proteins involved in developmental processes can serve as markers of developmental neurotoxicity.

  • 254.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Response to the comment on Viberg et al. (2008) "Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly" by Ching-Hung Hsu.2008In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 253, no 1-3, p. 154-154Article in journal (Refereed)
  • 255.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Changes in spontaneous behaviour and altered response to nicotine in the adult rat, after neonatal exposure to the brominated flame retardant, decabrominated diphenyl ether (PBDE 209)2007In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 28, no 1, p. 136-142Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), which are used as flame retardants, have recently been shown to increase in the environment and in human milk, which is also true for the decabrominated congener, 2,2′,3,3′,4,4′,5,5′,6,6′-decaBDE (PBDE 209). We have recently reported that neonatal exposure to PBDE 209 can induce persistent aberrations in spontaneous behaviour, in mice, effects that get worse with age. Other PBDE congeners affect learning and memory functions and the cholinergic system in adult mice and rats. The present study indicates that spontaneous behaviour, along with the cholinergic system during its developing stage, can be targets for PBDE 209 in the rat. Neonatal oral exposure of male Sprague–Dawley rats, on postnatal day 3, to 6.7, and 20.1 mg PBDE 209/kg body weight, was shown to disrupt normal spontaneous behaviour at 2 months of age. Also, rats exposed to the high dose of PBDE 209 showed a different response to adult nicotine treatment, compared to control rats. These findings show similarities to observations made from neonatal exposure of rats or mice to 2,2′,4,4′,5-pentaBDE (PBDE 99), 2,2′,4,4′,5,5′-hexaBDE (PBDE 153) and certain PCBs, compounds shown to affect both spontaneous behaviour and the cholinergic system. It is also clear from the present study and from recent studies from our research group that both lower and higher brominated diphenyl ethers can cause similar developmental neurotoxic effects in both mice and rats.

  • 256.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Deranged spontaneous behaviour and decrease in cholinergic muscarinic receptors in hippocampus in the adult rat, after neonatal exposure to the brominated flame-retardant, 2,2´, 4,4´, 5-pentabromodiphenyl ether (PBDE 99).2005In: Environmental Toxicology and Pharmacology, no 20, p. 283-288Article in journal (Refereed)
  • 257.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Developmental exposure to a brominated flame-retardant, 2,',4,4',5,5'-hexabromodiphenyl ether (PBDE 153) affects behaviour and cholinergic nicotinic receptors in brain of adult mice2002In: The Toxicologist, 2002Conference paper (Refereed)
  • 258.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Developmental neurotoxicity of PBDEs in mice and rats2005In: Toxicologist 84, 2005, p. 312-Conference paper (Refereed)
  • 259.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Eriksson, Per
    Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice2004In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 81, no 2, p. 344-353Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), one class of flame retardants used to suppress or inhibit the risk of fire, are regularly found in the environment and in human milk. The present study shows that neonatal exposure to a widely, environmentally found PBDE, 2,2',4,4',5-pentaBDE (PBDE 99), can induce developmental neurotoxic effects, such as changes in spontaneous behavior (hyperactivity), effects that are dose-response related and worsen with age. These changes are seen in C57/Bl mice of both sexes. Neonatal C57/Bl male and female mice were orally exposed on day 10 to 0.4, 0.8, 4.0, 8.0, or 16 mg PBDE 99/kg body weight. Spontaneous behavior (locomotion, rearing, and total activity) was observed in two-, five-, and eight-month-old mice. The behavior tests showed that the effects were dose-response and time-response related for both male and female mice. The observed developmental neurotoxic effects seen for PBDE 99, in C57/Bl mice, are similar to effects seen for 2,2',4,4'-tetraBDE (PBDE 47), PBDE 99, 2,2',4,4',5,5'- hexaBDE (PBDE 153), 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) and for certain PCBs, in male NMRI mice. Furthermore, the effects of PBDEs appear to be as potent in female mice as in male mice, and as potent in C57/Bl mice as in NMRI mice, concerning developmental neurotoxicity.

  • 260.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice.2003In: Toxicol Appl Pharmacol, ISSN 0041-008X, Vol. 192, no 2, p. 95-106Article in journal (Refereed)
  • 261.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Neonatal exposure to the brominated flame-retardant, 2,2´,4,4´,5-pentabromodiphenyl ether, decreases cholinergic nicotinic receptors in hippocamus and affects spontaneous behavoir in the adult mouse2004In: Environmental Toxicology and Pharmacology, Vol. 17, no 2, p. 61-65Article in journal (Refereed)
  • 262.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to the brominated flame-retardant, 2,2´,4,4´,5-pentabromodiphenylether, causes increased susceptibility in the cholinergic transmitter system at adult age.2002In: Toxicological Science, Vol. 67, p. 104-107Article in journal (Refereed)
  • 263.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neontal PBDE 99 exposure causes dose-response related behavioural derangements that are not sex or strain specific in mice2003In: The Toxicologist, 2003, p. 126-Conference paper (Refereed)
  • 264.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neurotixicity of different polybrominated diphenyl ethers, including PBDE 2092003In: Organohalogen Compounds, 2003, p. 65:9-11Conference paper (Other scientific)
  • 265.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neurotoxicity of different polybrominated diphenyl ethers, including PBDE 2092003In: Organohalogen compounds, 2003Conference paper (Other scientific)
  • 266.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    The link between adult  behavioral effects of  PBDEs and alterations in protein levels in the neonatal brain2010In: Organohalogen Compounds, ISSN 1026-4892, Vol. 72, p. 360-361Article in journal (Refereed)
  • 267.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jakobsson, Eva
    Örn, Ulrika
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brominated falme retardants: Uptake, retention and developmental neurotoxic effects of decabromodiphenylether (PBDE 209) in neonatal mouse.2001In: The Toxicologist, 2001Conference paper (Refereed)
  • 268.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jakobsson, Eva
    Örn, Ulrika
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brominated flame retardants: Uptake, retention and developmental neurotoxic effects of decabrominated diphenyl ether (PBDE 209) in neonatal mouse2001In: The Second International Workshop on Brominated Flame Retardants, May 14-16, Stockholm, Sweden, 2001Conference paper (Refereed)
  • 269.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jakobsson, Eva
    Örn, Ulrika
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Developmental neurotoxic effects of 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99) in the neonatal mouse2000In: The Toxicologist, 2000Conference paper (Refereed)
  • 270.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jakobsson, Eva
    Örn, Ulrika
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to hexabromodiphenyl ether (PBDE 153) affects behaviour and cholinergic nicotinic receptors in brain of adult mice2001In: The Second International Workshop on Brominated Flame Retardants, May 14-16, Stockholm, Sweden, 2001Conference paper (Refereed)
  • 271.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jakobsson, Eva
    Örn, Ulrika
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development.2003In: Toxicol Sci, ISSN 1096-6080, Vol. 76, no 1, p. 112-20Article in journal (Refereed)
  • 272.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Johansson, Niclas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Neonatal developmental neurotoxicity of decabrominated diphenyl ether, PBDE 209: a summary2007In: The Toxicologist, 2007Conference paper (Refereed)
  • 273.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Johansson, Niclas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Johan
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Decabrominated diphenyl ether (PBDE 209) induces neurotoxic effects in the neonatal and adult mouse after neonatal exposure2006In: The Toxicologist, 2006, p. 1455-Conference paper (Refereed)
  • 274.
    Viberg, Henrik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Johansson, Niclas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Psykiatri Ulleråker.
    Eriksson, Johan
    Marsh, G
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impaires spontaneous behavior and learning and memory functions of adult mice2006In: Toxicological Sciences, Vol. 92, p. 211-18Article in journal (Refereed)
  • 275.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Mundy, William
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to decabrominated diphenyl ether (PBDE 209) results in changes in BDNF, CaMKII and GAP-43, biochemical substrates of neuronal survival, growth, and synaptogenesis2008In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 1, p. 152-159Article in journal (Refereed)
    Abstract [en]

    Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3–4 weeks of life and reaching its peak around postnatal day 10. CaMKII, GAP-43 and BDNF play important roles during the BGS in mammals. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and increasing in the environment and in human milk, which is also true for the only congener still in use, decabrominated diphenyl ether (PBDE 209). In the present study, the brains from 1, 3, 7, 10, 14 and 28 days old mice, were analysed for CaMKII and GAP-43.The level of CaMKII increases continuously during the neonatal period, while GAP-43 has a bell-shaped ontogeny curve, which peaks around postnatal day 10, in mouse brain. Furthermore, the effects of PBDE 209 on the developmental expression of CaMKII, GAP-43 and BDNF were examined in mice. Neonatal NMRI-male mice were orally exposed on days 3–20.1 mg PBDE 209/kg body weight. The animals were euthanized 7 days after exposure to PBDE 209 and levels of CaMKII, GAP-43 and BDNF were analysed in different brain regions. The protein analysis showed that CaMKII increased significantly in hippocampus, but not in cortex, in animals 7 days after exposure to PBDE 209. GAP-43 showed a significant increase in hippocampus and a significant decrease in cortex of animals 7 days after exposure to PBDE 209. BDNF decreased significantly in hippocampus, but not in cortex, in mice 7 days after exposure to PBDE 209.This shows that PBDE 209 affects important proteins involved in normal maturation of the brain and further strengthen our findings concerning PBDE 209 as a developmental neurotoxicological agent.

  • 276.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Pontén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly2008In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 249, no 2-3, p. 153-9Article in journal (Refereed)
    Abstract [en]

    Ketamine, an anaesthetic agent used in newborns and toddlers, has been shown to induce neurodegeneration and alter adult behavior in mice, when administered during the neonatal period. Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. CaMKII and GAP-43 play important roles during the BGS in mammals. In the present study, 10 days old mice were exposed to 5-25 mg ketamine/kg bw and 24 h later brains were analyzed for calcium/calmodulin-dependent protein kinase II (CaMKII) and growth associated protein-43 (GAP-43) and at an age of 2 and 4 months the animals were tested for spontaneous behavior. The protein analysis showed that CaMKII increased significantly in hippocampus, but not in cortex, in animals 24h after exposure to ketamine. GAP-43 showed a significant increase in hippocampus, but a significant decrease in cortex for the highest ketamine dose. When looking at the adult behavior it was clear that neonatal ketamine exposure affected spontaneous behavior and habituation in a dose-response-related manner and that these behavioral disturbances were not transient but still persisted 2 months later. Taken together, this shows that ketamine affects important proteins involved in normal maturation of the brain and induce functional deficits in the adult individual, which further strengthen our findings concerning ketamine as a developmental neurotoxicological agent.

  • 277.
    Westin, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Piras, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Jansson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Dahlin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Brittebo, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Björk, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents2005In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 24, no 5, p. 565-573Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whether morphine can be transferred along the olfactory pathway to the CNS, thereby circumventingthe blood–brain barrier, after nasal administration to rodents. Radiolabelled and unlabelled morphine were administered via the right nostrilto mice and rats. Olfactory bulbs, brain tissue and blood samples were collected. Morphine-derived radioactivity was measured using liquidscintillation (LS) and the concentrations of morphine and its metabolite morphine-3-glucuronide (M3G) were also assessed with highperformanceliquid chromatography. The location of morphine-derived radioactivity in the rat brain was visualised by autoradiography.Overall, the levels of morphine in the right olfactory bulbs (ROBs) significantly exceeded those in the left olfactory bulbs (LOBs) and braintissue samples 15, 60 and 240 min after right-sided nasal administration. Fifteen minutes after intravenous administration, there were nosignificant differences between olfactory bulbs and the other brain areas. Five minutes after nasal administration, autoradiography revealedradioactivity surrounding the ROB and reaching one of the ventricles in the brain. After 60 min, radioactivity had reached the peripheral partsof the ROB. All the techniques used in this study demonstrate that morphine was transferred along the olfactory pathway to the CNS afternasal administration to rodents.

  • 278.
    Örberg, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Behaviour2007In: Reproductive Toxicology in Environmental Research: a report from the ReproSafe-programme, ISSN 0282-7298, Vol. Report 5729Article, review/survey (Other (popular scientific, debate etc.))
3456 251 - 278 of 278
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