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Developmental Neurotoxicity of Environmental Pollutants: Effects on neuronal protein markers after neonatal exposure
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
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 [en]
Developmental neurotoxicity, Neonatal exposure, Protein markers, Environmental pollutants
National Category
Biological Sciences
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-213017OAI: oai:DiVA.org:uu-213017DiVA: diva2:680247
Opponent
Supervisors
Available from: 2014-01-08 Created: 2013-12-17 Last updated: 2014-07-24Bibliographically approved
List of papers
1. A single exposure to bisphenol A alters the levels of important neuroproteins in adult male and female mice
Open this publication in new window or tab >>A single exposure to bisphenol A alters the levels of important neuroproteins in adult male and female mice
2012 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 33, no 5, 1390-1395 p.Article in journal (Refereed) Published
Abstract [en]

Bisphenol A (BPA) is widely used in polymer products in food and beverage containers, baby bottles, dental sealants and fillings, adhesives, protective coatings, flame retardants, water supply pipes, and compact discs, and is found in the environment and in placental tissue, fetuses and breast milk. We have recently reported that a single neonatal exposure to bisphenol A can induce persistent aberrations in spontaneous behavior, in a dose-dependent manner, and affect the adult response to the cholinergic agent nicotine. Furthermore, other recent reports indicate that pre- and perinatal exposure to bisphenol A can induce neurotoxic effects. The present study indicates that a single neonatal exposure to bisphenol A, on postnatal day 10, during the peak of the brain growth spurt, can alter the adult levels of proteins important for normal brain development (CaMKII and synaptophysin). These alterations are induced in both male and female mice and effects are seen in both hippocampus and cerebral cortex. These results further support our recent study showing that neonatal exposure to bisphenol A can act as a developmental neurotoxicant and the effects are similar to effects seen after a single postnatal exposure to other POPs, such as PBDEs, PCBs and PFCs.

Keyword
Bisphenol A (BPA), Neonatal, Developmental neurotoxicity, CaMKII, Synaptophysin
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-187101 (URN)10.1016/j.neuro.2012.09.002 (DOI)000310396600047 ()
Available from: 2012-12-04 Created: 2012-12-03 Last updated: 2017-12-07Bibliographically approved
2. A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain
Open this publication in new window or tab >>A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain
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. 

Keyword
Perfluorohexane sulfonate (PFHxS), Neonatal, Developmental neurotoxicity, CaMKII, GAP-43, Synaptophysin, Tau
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-204997 (URN)10.1016/j.neuro.2013.05.007 (DOI)000321413400023 ()
Available from: 2013-08-14 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved

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