WONG CHEN, MARK DODO
(2013)
Cognitive Impairment in Mice Exposed to Environmental Arsenic and Discuss Its Relation to Public Health.
Master Essay, University of Pittsburgh.
Abstract
Arsenic toxicity is one of World Health Organization’s ten chemicals of major public health concern. Arsenic and arsenic compounds have been classified as a group one human carcinogen by the International Agency for Research on Cancer (IARC), who stated that arsenic in drinking-water is carcinogenic to humans. It is estimated that around 150 million people in seventy countries are exposed to naturally existing arsenic in polluted drinking water, and approximately sixty million people are under chronically constant exposure in Asia. Children, particularly in in utero or during perinatal phases, may be much more susceptible and have a higher predisposition to health effects from arsenic exposure than adults. The aim of this study is to find out how environmental level exposure to arsenic during the in utero phase brings alterations in epigenomic landscapes, and includes observation of differences in intellectual performance in adult mice exposed to arsenic. Since histone acetylation is dynamical and reversible, the experimental results from mice might set up references for applying to human communities that bring more knowledge for children and general public who have already been exposed to constant arsenic exposure. The study group exposed C57BL6/J mice to 100 μg/L arsenic-contaminated water, starting one week before onset of breeding and though out the entire gestational period.. Then, chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-seq) was done to identify H3K9 acetylation patterns in the offspring of both the exposed and the control groups. In embryos exposed to arsenic, the arsenic caused global hypo-acetylation at H3K9 and altered functional annotation in brain tissue of the exposed mice’s offspring. The study group also discovered that adult mice exposed to arsenic experienced impaired spatial and episodic memory, as well as deteriorated fear conditioning performance. The study results are the first to demonstrate how prenatal arsenic exposure brings genome wide changes in H3K9 acetylation pattern in a mice offspring; and discover an association between moderate arsenic exposure and cognitive impairment in adult mice.
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