The artificial sweetener Splenda intake promotes changes in expression of c-Fos and NeuN in hypothalamus and hippocampus of rats

Background: Obesity is the result of the interaction of multiple variables, including the excessive increase of sugar-sweetened beverages consumption. Diets aimed to treat obesity have suggested the use of artificial sweeteners. However, recent evidence has shown several health deficits after intake of artificial sweeteners, including effects in neuronal activity. Therefore, the influence of artificial sweeteners consumption such as Splenda, on the expression of c-Fos and neuronal nuclear protein (NeuN) in hypothalamus and hippocampus remains to be determined. Objectives: We investigated the effects on c-Fos or NeuN expression in hypothalamus and hippocampus of Splenda-treated rats. Methods: Splenda was diluted in water (25, 75 or 250 mg/100 mL) and orally given to rats during 2 weeks ad libitum. Next, animals were sacrificed by decapitation and brains were collected for analysis of c-Fos or NeuN immunoreactivity. Results: Consumption of Splenda provoked an inverted U-shaped dose-effect in c-Fos expression in ventromedial hypothalamic nucleus while similar findings were observed in dentate gyrus of hippocampus. In addition, NeuN immunoreactivity was enhanced in ventromedial hypothalamic nucleus at 25 or 75 mg/100 mL of Splenda intake whereas an opposite effect was observed at 250 mg/100 mL of artificial sweetener consumption. Lastly, NeuN positive neurons were increased in CA2/CA3 fields of hippocampus from Splenda-treated rats (25, 75 or 250 mg/100 mL). Conclusion: Consuming Splenda induced effects in neuronal biomarkers expression. To our knowledge, this study is the first description of the impact of intake Splenda on c-Fos and NeuN immunoreactivity in hypothalamus and hippocampus in rats.