In vitro developmental neurotoxicity of acrylamide

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MARC

Attoff, Kristina,1985-Stockholms universitet,Institutionen för neurokemi (author)

In vitro developmental neurotoxicity of acrylamide

BookEnglish2016

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Stockholm :Department of Neurochemistry, Stockholm University,2016
55 s.
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:su-128755
ISBN:9789176494134
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-128755URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:vet swepub-contenttype
Subject category:lic swepub-publicationtype

Notes

The number of children with neurodevelopmental disorders is increasing worldwide which makes it a public concern. Exposure to environmental chemicals has been reported as a source of developmental neurotoxicity. There is also an increase in the number of chemicals reaching the global market each year and currently there are thousands of substances that have not yet been tested for developmental neurotoxicity. The current developmental neurotoxicity testing guidelines are time consuming, expensive, require a lot of animals and have relatively low sensitivity understanding for the mechanisms of toxicology. The field of developmental neurotoxicity testing is in need of a paradigm shift to the use of alternative in vitro methods capable of testing and screening large number of substances. The next generation developmental neurotoxicity testing will consist of both in silico and in vitro testing that has to be used in a combined fashion so that it will generate a more rapid and efficient toxicity testing. The methods need to be standardized between laboratories so that reproducible data can be obtained. Simple endpoints will simply not be enough for in vitro developmental neurotoxicity testing models. Rather, a battery of more refined endpoints that pinpoints the specific toxicity of a compound, discriminate between different neural subpopulations and different stages of neural differentiation is crucial for success. The use of mRNA biomarkers could be a good example of such an endpoint, and have been suggested to be valuable in detecting developmental neurotoxicity. This thesis will give a broad overview of different alternative in vitro models for developmental neurotoxicity. Developmental neurotoxicity of acrylamide was investigated by using selected cell models and endpoints. Acrylamide is a well-known neurotoxic compound and most people get exposed to the compound by food consumption and from environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed and the risk for adverse effects in the developing nervous system is overwhelming. The neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as indicators for developmental neurotoxicity. The reduced neurite outgrowth in the SH-SY5Y cell model occurred at up to seven orders of magnitude lower than what have been previously shown for different neural cell systems. Acrylamide also affected the differentiation process in both neurons and glia cells in the C17.2 cell line. We show that acrylamide attenuated neural differentiation at seven orders of magnitude lower concentrations than the estimated plasma concentration of free acrylamide in the fetus. The fact that low concentrations seem to delay the differentiation process in both cell lines, raises cause for an alarm for developmental neurotoxicity induced by acrylamide.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
neurokemi med molekylär neurobiologi
Neurochemistry with Molecular Neurobiology

Added entries (persons, corporate bodies, meetings, titles ...)

Forsby, Anna,DocentStockholms universitet,Institutionen för neurokemi(Swepub:su)annaf (thesis advisor)
Östlund Farrants, Ann-Kristin,ProfessorStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut (opponent)
Stockholms universitetInstitutionen för neurokemi (creator_code:org_t)

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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-128755

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