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A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
2013 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 37, 190-196 p.Article in journal (Refereed) Published
Abstract [en]

Perfluorohexane sulfonate (PFHxS) is an industrial chemical and belongs to the group of perfluorinated compounds (PFCs). It has recently been shown to cause developmental neurobehavioral defects in mammals. These compounds are commonly used in products such as surfactant and protective coating due to their ability to repel water- and oil stains. PFCs are globally found in the environment as well as in human umbilical cord blood, serum and breast milk. In a previous study on other well-known PFCs, i.e. PFOS and PFOA, it was shown that neonatal exposure caused altered neuroprotein levels in the hippocampus and cerebral cortex in neonatal male mice. The present study show that neonatal exposure to PFHxS, during the peak of the brain growth spurt, can alter neuroprotein levels, e.g. CaMKII, GAP-43, synaptophysin and tau, which are essential for normal brain development in mice. This was measured for both males and females, in hippocampus and cerebral cortex. The results suggest that PFHxS may act as a developmental neurotoxicant and the effects are similar to that of PFOS and PFOA, but also to other substances such as PCBs, PBDEs and bisphenol A. 

Place, publisher, year, edition, pages
2013. Vol. 37, 190-196 p.
Keyword [en]
Perfluorohexane sulfonate (PFHxS), Neonatal, Developmental neurotoxicity, CaMKII, GAP-43, Synaptophysin, Tau
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-204997DOI: 10.1016/j.neuro.2013.05.007ISI: 000321413400023OAI: oai:DiVA.org:uu-204997DiVA: diva2:640854
Available from: 2013-08-14 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Developmental Neurotoxicity of Environmental Pollutants: Effects on neuronal protein markers after neonatal exposure
Open this publication in new window or tab >>Developmental Neurotoxicity of Environmental Pollutants: Effects on neuronal protein markers after neonatal exposure
2013 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis focused on investigations of the developmental neurotoxic effects of bisphenol A (BPA) or perfluorohexane sulfonate (PFHxS), after a single neonatal exposure, during a critical period of the brain development in mice.

BPA is a well-known industrial chemical used in the production of polymer products and PFHxS is used as an industrial additive as a surfactant. Commonly, these two compounds have been found in the environment, wild-life and in humans. They are a cause of concern as BPA is known to be an endocrine disrupter and PFHxS is presently unregulated; although similar compounds have been phased-out of production. Additionally, humans may be exposed to these compounds throughout their life time starting already before birth. Infants and children are especially vulnerable as they are not yet fully developed and therefore can be more sensitive to toxic insults. The brain growth spurt (BGS), is a critical period of the mammalian brain development, and is characterized by a rapid growth as well as biochemical changes. Toxic insults during this period have shown to cause persistent and irreversible behavioral and cognitive dysfunctions in mice. The onset and duration of the BGS varies between species, and in mice it is postnatal starting from birth and spans up to 3-4 weeks of life. In humans, it starts from around the third trimester and extends up to the first two years of life. For both species the BGS coincide with the period of lactation. The BGS process involves several important neuroproteins, such as BDNF, CaMKII, GAP-43, synaptophysin and tau. These neuroproteins are essential for maintaining normal neuronal growth and synaptogenesis. Additionally, these proteins display specific ontogenic patterns and peak during the BGS in the neonatal mouse brain.

This thesis has shown that BPA and PFHxS can cause developmental neurotoxic effects when administered directly during the peak of the BGS. BPA induced altered levels of CaMKII and synaptophysin in adult mice, whereas PFHxS induced altered levels of CaMKII, GAP-43, synaptophysin and tau in neonatal mice. These effects are similar to previously studied persistent organic pollutants such as polybrominated diphenyl ethers (PBDEs) and other perfluorinated compounds (PFCs). The altered neuroprotein levels may be a plausible explanation to recently seen disarranged behavior in adult mice neonatally exposed to BPA or PFHxS. As the two compounds are seemingly different, but produce similar neurotoxic effect, it further supports the notion that the developing brain is sensitive to toxic insults when exposed during a sensitive period of brain development. Also, further investigations on finding mechanisms of action and biomarkers for toxic insult of environmental pollutants are important in order to be able to foresee and prevent future consequences of existing and new emerging substances.

Place, publisher, year, edition, pages
Uppsala: Uppsala University, Department of Organismal Biology, 2013. 37 p.
Keyword
Developmental neurotoxicity, Neonatal exposure, Protein markers, Environmental pollutants
National Category
Biological Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-213017 (URN)
Opponent
Supervisors
Available from: 2014-01-08 Created: 2013-12-17 Last updated: 2014-07-24Bibliographically approved
2. Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
Open this publication in new window or tab >>Developmental neurotoxicity of persistent and non-persistent pollutants: Behavioral and neurochemical assessments of a perfluorinated compound, pesticides and interaction effects
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The focus of this thesis was to investigate developmental neurotoxic effects of different persistent and non-persistent environmental pollutants, alone or in binary mixtures, when exposure occurs during a critical period of brain development, in mice. The compounds investigated included a perfluorinated compound, perfluorohexane sulphonate (PFHxS), and four different pesticides, endosulfan, cypermethrin, chlorpyrifos and carbaryl.

Both persistent and non-persistent pollutants are detected in the environment and in humans, which shows that exposure to these compounds is occurring in real life. Humans can therefore be exposed to various pollutants during their whole lifetime, starting from the gestational period to adulthood. Furthermore, exposure to environmental pollutants is rarely exclusive to a single compound, but rather occurs through combinations of various pollutants present in the environment. Exposure to environmental pollutants during human brain development have been suggested to be a possible cause for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous studies have shown that chemicals can induce irreversible disorders in brain function when exposure to these chemicals occurs during a critical defined period of the brain development known as the brain growth spurt (BGS). The BGS is characterized by a rapid growth and development of the immature brain. In humans, and mice, this period also overlaps the lactation period indicating that newborns and toddlers can be exposed via mothers’ milk as well.

This thesis has shown that a single oral exposure to PFHxS, endosulfan, cypermethrin, chlorpyrifos or carbaryl can induce developmental neurotoxic effects in mice, when exposure occurs during a critical period of brain development. These effects are manifested as persistent altered adult spontaneous behavior in a novel home environment, modified habituation, altered susceptibility of the cholinergic system and changed levels of neuroproteins in the mouse brain. Furthermore, a single neonatal co-exposure to a binary mixture of carbaryl/chlorpyrifos or PFHxS/endosulfan can interact and exacerbate the adult behavioral effects. These effects were seen at dosages were the single compound did not elicit a response or induced a much weaker behavioral effect. This indicates that risk assessments conducted on single compounds might underestimate interaction effects of mixtures when co-exposed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1283
Keyword
Brain, Neonatal, Mixtures, Cholinergic system, Organochlorines, Pyrethroids, Organophosphates, Carbamates, Insecticides, PFCs, PFAAs, PFHxS, Endosulfan, Cypermethrin, Chlorpyrifos, Carbaryl
National Category
Natural Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-261742 (URN)978-91-554-9326-4 (ISBN)
Public defence
2015-10-23, Zootissalen, EBC, Villavägen 9, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2015-10-02 Created: 2015-09-03 Last updated: 2015-10-05

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Lee, IwaViberg, Henrik

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