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Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice
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: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 244, no 2-3, 157-165 p.Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies have shown a discrepancy between children in the Faeroe Islands and children in the Seychelles with regard to neuropsychological defects during early development. Both populations have a high consumption of MeHg-contaminated fish. The defective neuropsychological differences seen in children from the Faeroe Islands could be attributed to PCBs via the mother's dietary consumption of whale meat and blubber in addition to MeHg. We have previously reported that certain persistent environmental toxicants like PCBs, DDT and PBDEs can induce permanent developmental neurotoxic effects in mice when these agents are present during a critical period of the neonatal brain development. The present study investigates whether PCB 153 (an ortho-substituted PCB) can interact with MeHg to enhance developmental neurotoxic effects on spontaneous behavior and habituation. Neonatal NMRI male mice were exposed at 10 days of age to a single oral dose of one of the following doses: PCB 153 (1.4 μmol/kg body weight), MeHg (0.08, 0.40, or 4.0 mg/kg body weight), PCB 153 plus MeHg, or a vehicle (20% fat emulsion). Spontaneous behavior, habituation, and cognitive function were observed in 2- and 4-month-old mice. The present study demonstrates that an interaction from co-exposure to low doses of PCB 153 and MeHg enhances developmental neurotoxic effects. These effects are manifested as disrupted spontaneous behavior, lack of habituation, and reduced cognitive functions. These effects occur at doses within the same order of magnitude as reported for exposed children.

Place, publisher, year, edition, pages
2008. Vol. 244, no 2-3, 157-165 p.
Keyword [en]
PCB, PCB 153 (2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl), Methyl mercury, Behavior, Habituation, Neonatal, Neurotoxicity
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96659DOI: 10.1016/j.tox.2007.11.006ISI: 000253942700007PubMedID: 18155821OAI: oai:DiVA.org:uu-96659DiVA: diva2:171307
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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