Objective To explore the effects of individual and combined exposure to fluoride and arsenic on cAMP response element binding protein (CREB) in brain of rats.
Methods Thirty-two male Sprague-Dawley rats at the beginning of weaning were randomly divided into 4 groups: 3 groups of rats were exposed to 120 mg/L sodium fluoride (NaF), 70 mg/L sodium arsenite (NaAsO2), or 120 mg/L NaF + 70 mg/L NaAsO2 mixed solution for 90 days, respectively; 1 control group of rats drank distilled water for 90 days. The mRNA expression levels of CREB and protein expression levels of CREB and phosphorylated CREB (p-CREB) in cerebral cortex and hippocampus of rats were detected by real-time polymerase chain reaction and Western blot assay, respectively.
Results Compared with the controls, the CREB mRNA expression levels in cerebral cortex and hippocampus in the 3 exposure groups were markedly decreased (P < 0.05). The CREB mRNA expression level in hippocampus of co-exposed rats was lower than that in the NaF-exposed or NaAsO2-exposed rats. The p-CREB protein expression levels in cerebral cortex and hippocampus were 0.68& #177;0.16 and 0.68& #177;0.15 respectively for the NaF-exposed rats, 0.46& #177;0.13 and 0.48& #177;0.11 for the NaAsO2-exposed rats, as well as 0.38& #177;0.11 and 0.31& #177;0.14 for the co-exposed rats, respectively; all were significantly lower than those of the controls (0.83& #177; 0.06, 0.80& #177;0.11, respectively) (P < 0.05). Compared with the NaF-exposed rats, the p-CREB protein expression level in cerebral cortex and hippocampus in the NaAsO2-exposed rats were decreased (P < 0.05). The p-CREB protein expression level in hippocampus in the co-exposed rats was statistically lower than that in the NaF-exposed or the NaAsO2-exposed rats (P < 0.05).
Conclusion Fluoride, arsenic, and co-exposure to both chemicals may down-regulate the expression levels of CREB mRNA and protein phosphorylation in the cerebral cortex and hippocampus of rats.