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Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult 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: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 1, 160-169 p.Article in journal (Refereed) Published
Abstract [en]

Perfluorinated compounds (PFCs) are found in applications such oil/water repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants and fire extinguishers. PFCs are persistent in the environment. They have been found in humans and in wildlife.

We reported earlier that persistent organic pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic defects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system in adults, when mice were exposed during a critical period of neonatal brain development.The present study was conducted to see whether PFCs can cause similar developmental neurotoxic effects as earlier observed for POPs as PCBs and PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21 μmol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The control animals received in the same manner 10 ml/kg body weight of the 20% fat emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total activity), and habituation were observed in 2- and 4-month-old mice. The susceptibility of the cholinergic system was explored in a nicotine-induced spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack of habituation and hyperactivity in adult mice. These effects were also seen to worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic system, manifested as a hypoactive response to nicotine, compared to a hyperactive response to nicotine in controls. These developmental neurotoxic effects are similar to those we reported earlier for PCBs and PBDEs. This suggests that PFOS and PFOA be included in the group of POPs known to be developmental neurotoxicants.

Place, publisher, year, edition, pages
2008. Vol. 29, no 1, 160-169 p.
Keyword [en]
PFC, PFOS, PFOA, PFDA, Developmental neurotoxicity, Behaviour
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-12791DOI: 10.1016/j.neuro.2007.10.008ISI: 000253187600019PubMedID: 18063051OAI: oai:DiVA.org:uu-12791DiVA: diva2:40560
Available from: 2008-06-12 Created: 2008-06-12 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Neonatal Exposure to Highly Brominated Diphenyl Ethers and Perfluorinated Compounds: Developmental Dependent Toxicity and Interaction
Open this publication in new window or tab >>Neonatal Exposure to Highly Brominated Diphenyl Ethers and Perfluorinated Compounds: Developmental Dependent Toxicity and Interaction
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis investigated the developmental neurotoxic effects of neonatal exposure to highly brominated diphenyl ethers (PBDEs) and perfluorinated compounds (PFCs), alone or in combinations, during a critical period of the brains’ rapid growth and development, in mice. The compounds investigated were the decaBDE (PBDE 209), nonaBDE (PBDE 206), octaBDE (PBDE 203), heptaBDE (PBDE 183), and three PFCs, PFOS, PFOA, and PFDA.

PBDEs and PFCs have been identified as emerging classes of persistent environmental compounds, present in wildlife as well as humans, and present at higher levels in infants/children, compared to older persons. Individuals can be exposed to these compounds throughout her/his lifetime and newborn/children can be exposed to toxicants both via the mothers’ milk and directly via ingestion and inhalation.

The brain growth spurt (BGS) is defined by rapid growth and developmental of the brain. For rodents (mice and rats), the BGS is postnatal spanning the first 3-4 weeks after birth. In humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. It has been shown that several environmental toxicants can induce permanent disorders in brain function when administered to the neonatal mouse, during the BGS.

This thesis shows that highly brominated PBDEs, including PBDE 209, PBDE 206, and PBDE 203 can cause developmental neurotoxic effects, when given directly to the neonatal mouse. Of the investigated PFCs, PFOS and PFOA were shown to cause similar effects as the PBDEs. Furthermore, PBDE 209 and PFOA can at low doses interact and enhance the neurotoxic effects in mice. Effects in the adult animal included; deranged spontaneous behavior, reduced or lack of habituation, decreased learning and memory abilities, and increased susceptibility of the cholinergic system. Both classes of compounds were shown to affect proteins (CaMKII, GAP-43, synaptophysin, and tau) important for neuronal growth and synaptogenesis in the neonatal mouse brain.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 619
National Category
Biological Sciences
Research subject
Ecotoxicology
Identifiers
urn:nbn:se:uu:diva-99255 (URN)978-91-554-7456-0 (ISBN)
Public defence
2009-04-24, Lindahlsalen, EBC, Norbyvägen 18A, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2009-04-02 Created: 2009-03-11 Last updated: 2009-09-04Bibliographically approved

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Johansson, NiclasFredriksson, AEriksson, Per

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