Abstract
Arsenic is carcinogenic and teratogenic. In addition, it is also a developmental neurotoxicant. Little is known however about the effect of arsenic exposure during brain development on social behavior. This study aimed to detect the effect of developmental arsenic exposure on social behavior and related gene expression in C3H adult male mice. Pregnant C3H mice were exposed to sodium arsenite (NaAsO2, 85 ppm in the drinking water) from gestational day (GD) 8 to 18. The F1 generation male pups from different mothers were taken and social behavior tasks were examined. Social behavioral-related gene expression in the prefrontal cortex was determined by the real-time RT-PCR method. The mice with developmental arsenic exposure showed poor sociability and poor social novelty preference. Glutamate receptor expression (NMDA and AMPA receptor subunits) showed no significant difference, but gene expressions of serotonin receptor 5B (5-HT 5B) and brain-derived neurotrophic factor (BDNF) were significantly decreased (p < 0.05) in the arsenic-exposed group compared to control group. The heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) gene expressions were not significantly different. Our findings indicate that developmental arsenic exposure might affect social behavior by modulating serotonin receptors and reducing BDNF. Some oxidative stress markers and inflammatory markers were not affected.
Highlights
Arsenic is a naturally occurring metalloid and can be found in water as the inorganic form [1]
This study aimed to detect the effect of developmental arsenic exposure on social behavior and related gene expression in the prefrontal cortex of C3H adult male mice
The reasons for selection of a 85 ppm dose of NaAsO2 are: (1) species differences were observed between human and mouse and a high dose is required for detection of neurotoxic effects in C3H mice and no maternal toxicity and teratogenicity were observed at the dose of present study; (2) this is a standard dose to detect the effects of developmental exposure to arsenic on neurotoxicity, reproductive toxicity and carcinogenicity in our research group [22,32,33]
Summary
Arsenic is a naturally occurring metalloid and can be found in water as the inorganic form (arsenite or arsenate) [1]. Arsenic contamination in drinking water is a worldwide problem, especially in Bangladesh. According to the study of Ahmad et al, 50 million people in Bangladesh were exposed to arsenic-contaminated water (above 0.05 mg/L) and the highest level of contamination is 2.97 mg/L [2]. In 2012, it was estimated that about 19 million people in Bangladesh were still exposed to arsenic concentrations above the national standard of 0.05 mg/L. Health Organization provisional guideline value (0.01 mg/L), about 39 million people in Bangladesh were exposed to arsenic-contaminated water [3]. There are several health problems related to arsenic exposure; skin lesions, cardiovascular disease, neurological disorders, and diabetes [4,5,6]. Arsenic is a well-known carcinogen and it has been widely studied as a human carcinogenic agent. Arsenic has embryotoxicity and teratogenicity effects [7,8]
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