Abstract
Highlights
- Fluoride and arsenic exposure decrease the ability of learning and memory.
- Found changes in the level of protein expression about ERK/CREB on rat pups.
- It was found that the potential synergetic effect of fluoride and arsenic.
Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100 mg/L), sodium arsenite (75 mg/L), and a sodium fluoride (100 mg/L) and sodium arsenite (75 mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the hippocampus and cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in PND42 pups, and p-CREB expression in the cerebral cortex was decreased in PND21 pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage decreases ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure.