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Co-exposure of neonatal mice to a flame retardant PBDE 99 (2,2',4,4',5-pentabromodiphenyl ether) and methylmercury enhances developmental neurotoxic defects
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
2008 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 101, no 2, 275-285 p.Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies indicate that exposure to environmental pollutants during early human development can have deleterious effects on cognitive development. The interaction between environmental pollutants is suggested as one reason for the observed defective neurological development in children from the Faeroe Islands as compared to children from the Seychelles. We have previously seen in mice that polychlorinated biphenyls (PCBs) can interact together with methyl mercury (MeHg), as well as PCB together with polybrominated diphenyl ether (PBDE 99) to exacerbate developmental neurotoxic effects when present during a critical period of neonatal brain development. PBDEs are a new class of global environmental contaminants. The present study shows that neonatal coexposure to PBDE 99 (0.8 mg/kg body weight) and MeHg (0.4 or 4.0 mg/kg body weight) can exacerbate developmental neurotoxic effects. These effects are manifested as disrupted spontaneous behavior, reduced habituation, and impaired learning/memory abilities. This is seen in the low dose range, where the sole compounds do no give rise to developmental neurotoxic effects. The effects seen are more than just additive. Furthermore, a significant effect of interaction was seen on the cholinergic nicotinic receptors in the cerebral cortex and hippocampus. This suggests that a mechanism for the observed cognitive defects is via the cholinergic system. Furthermore, PBDE can interact with MeHg causing developmental neurotoxic effects similar to those we previously have observed between PCB 153 + MeHg and PCB 52 + PBDE 99. This is of vital importance, as the levels of PBDEs are increasing in mother's milk and in the environment generally.

Place, publisher, year, edition, pages
2008. Vol. 101, no 2, 275-285 p.
Keyword [en]
PBDE, methyl mercury, behavior, cholinergic receptors, neonatal, neurotoxicity
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96661DOI: 10.1093/toxsci/kfm271ISI: 000252306100010PubMedID: 17982161OAI: oai:DiVA.org:uu-96661DiVA: diva2:171309
Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Developmental Neurotoxicity in Mice Neonatally Co-exposed to Environmental Agents: PCB, PBDE, Methyl Mercury and Ionized Radiation - Interactions and Effects
Open this publication in new window or tab >>Developmental Neurotoxicity in Mice Neonatally Co-exposed to Environmental Agents: PCB, PBDE, Methyl Mercury and Ionized Radiation - Interactions and Effects
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis investigates the neurotoxic effects in mice neonatally co-exposed to different toxic environmental agents during a defined critical period of the brains's rapid growth and development.

Environmental toxic agents are incorporated in our environment. The agents investigated in this thesis are ortho-substituted polychlorinated biphenyls (PCBs 52, and 153), co-planar PCB (PCB 126), polybrominated diphenyl ether (PBDE 99), methyl mercury (MeHg), and γ-radiation. Several epidemiological studies show that human exposure to environmental agents during early development can affect childhood cognitive development.

The brain growth spurt (BGS) is defined by rapid growth and development of the immature brain. For rodents (rats and mice) the BGS is postnatal spanning the first 3-4 weeks after birth. For humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. Several studies have shown that the BGS period of the brain's development renders the brain vunerable and susceptible to insults caused by environmental agents.

The combinations of environmental agents used in this thesis were: PCB 52 + PBDE 99, PCB 153 + MeHg, PCB 126 + MeHg, PBDE 99 + MeHg, and γ-radiation + MeHg. The studies presented in this thesis show that co-exposure to low doses of environmental agents lead to interaction effects. These effects of interaction include defective spontaneous behavior, diminished habituation capabilities and hyperactive condition, decreased learning and memory abilities, and reduction in the nicotinic cholinergic receptor densities.

Traditionally environmental agents are evaluated one at a time to investigate their effects of toxicity. This thesis indicates that the effects of interaction caused by co-exposure were often seen at doses where exposure to the individual environmental agent alone did not cause any effect. The observed effect of co-exposure were often as pronounced as a dose up to ten times the individual environmental agent alone.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 387
Keyword
Biology, PCB, PBDE, MeHg, ionized radiation, neonatal, development, neurotoxicity, behavior, cholinergic system, Biologi
Identifiers
urn:nbn:se:uu:diva-8416 (URN)978-91-554-7071-5 (ISBN)
Public defence
2008-02-09, Lindahlsalen, EBC, Norbyvägen 18A, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2009-04-02Bibliographically approved

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