4.2 Article

Risk of neurodegenerative disease due to tau phosphorylation changes and arsenic exposure via drinking water

Journal

TOXICOLOGY RESEARCH
Volume 10, Issue 2, Pages 292-298

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxres/tfab011

Keywords

arsenic; tau; phosphorylation; neurodegenerative disease; Alzheimer; water contamination

Categories

Funding

  1. Isfahan University of Medical Sciences and Pharmaceutical Research Center [396772]

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The study showed that arsenic exposure led to accumulation of arsenic in the brain and significant increases in tau protein phosphorylation at the Ser262 site, potentially increasing the risk of neurodegenerative diseases.
It is estimated that around 140 million people are drinking highly contaminated water with arsenic (As) as a natural earth's crust component. On the other hand, the prevalence of neurodegenerative disorders, especially Alzheimer's disease, is constantly increasing. The aim of the present study was to investigate the correlation between oral arsenic trioxide exposure and its impact on tau protein phosphorylation at Ser262. Fifty-four male mice were randomly divided into three groups and were freely accessed to food and contaminated water of 1 and 10 ppm arsenic trioxide for 3 months, except for control subjects. At the end of each month, As concentration and tau phosphorylation were checked with graphite furnace atomic absorption spectrometer and western blot analysis, respectively. Surprisingly, it was observed that the amount of measured brain arsenic in 10 ppm-exposed subjects was significantly increased after 3 months (P-value < 0.0001). The significant changes in tau phosphorylation were not seen in the 1 ppm-exposed subjects, and it was observed that Ser262 phosphorylation significantly increased after 2 and 3 months in the 10 ppm group (P-value < 0.05). Our results demonstrated that arsenic accumulated in the brain time-dependently and increased Ser262 tau phosphorylation, which is very important in several tauopathies. In conclusion, it could be inferred that environmental arsenic exposure even at very low concentrations could be considered as a reason for increasing the risk of developing neurodegenerative disease.

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