Abstract
A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals. Perinatal exposures to toxic chemicals have been reported to exert an inhibitory effect on mouse neural development and behaviors. However, the effect of combined exposures of organophosphate and nicotine has not been previously reported. In this study, we investigated whether a combined exposure of diazinon and nicotine can have a synergistic effect. The effects of the combined chemical exposure on cell viability and neuronal differentiation were examined using mouse Sox1-GFP cells. Additionally, mice were maternally administered 0.18 mg/kg diazinon, a no adverse effect level (NOAEL) dose, combined with 0.4, 1, and 2 mg/kg nicotine. Mice offspring underwent behavior tests to assess locomotor, depressive, cognitive, and social behaviors. Morphological change in the brain was investigated with immunolocalization. We revealed that the combined exposure to diazinon and nicotine can have a synergistic adverse effect in vitro. In addition, the chemical-treated mouse offspring showed abnormalities in motor learning, compulsive-like behaviors, spatial learning, and social interaction patterns. Moreover, 0.18 mg/kg diazinon and 2 mg/kg nicotine co-exposure resulted in an increase in tyrosine hydroxylase (TH)-positive dopaminergic neurons. Thus, the findings suggest that perinatal co-exposure to nicotine and diazinon can result in abnormal neurodevelopment and behavior, even at low-level administration.
Highlights
Published: 20 July 2021During pregnancy, maternal exposure to a specific chemical compound may result in abnormal brain development and behavior in humans and animals, and the real-life environment during pregnancy can involve multiple and simultaneous exposures to toxic chemicals, such as pesticides and cigarette smoke
The chemical-containing medium was prepared at six different concentrations, from 10−5 M to 1 M of nicotine combined with 10−5 M of diazinon, respectively (Figure 1E,F)
There were no significant differences between the combined chemical-treated group and nicotine only-treated group (Figure 1B,D,F)
Summary
Maternal exposure to a specific chemical compound may result in abnormal brain development and behavior in humans and animals, and the real-life environment during pregnancy can involve multiple and simultaneous exposures to toxic chemicals, such as pesticides and cigarette smoke. In this regard, synergistic adverse effects generated by co-exposure of toxicants have attracted contemporary researchers. A combination of benzopyrene and lead (Pb) can produce a synergistic adverse effect on spatial learning and memory impairments by exacerbating oxidative stress [2]. Combined exposure to multiple substances may enhance or counterbalance the toxicity of chemicals, leading to unknown risks to animal health
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