High-dose dibutyl phthalate improves performance of F1 generation male rats in spatial learning and increases hippocampal BDNF expression independent on p-CREB immunocontent

Abstract

Dibutyl phthalate (DBP), an important representative of endocrine disrupting chemical, is suspected of affecting the cognitive function of humans and animals. In this study, effects of DBP on maze performance in male rats were evaluated by spatial learning tasks; the effects of DBP on the expression of brain-derived neurotrophic factor (BDNF) were also analyzed in both mRNA and mature protein levels in the hippocampus, with intent to investigate the possible mechanism underlying the behavioral findings. Pregnant Wistar rats were treated orally by gavage with 0, 25, 75, 225 and 675 mg DBP/kg BW/day from gestational day (GD) 6 to postnatal day (PND) 21, and then the weaned offspring continued receiving the same treatment till PND 28. We found that male pups treated with high-dose DBP showed enhancement in spatial acquisition in a Morris water maze during PNDs 30–33, and displayed better retention of spatial memory in a probe trial after a reverse trail during PNDs 60–62. Real-time PCR and western blotting analysis of the hippocampus from DBP-treated male rats on PND 21 revealed an increase in BDNF expression, compared to the vehicle-matched control. BDNF variant III, a transcription promoted by active CREB (i.e. p-CREB), as well as the immunocontent of p-CREB, was scarcely altered by the treatment. Our results suggest that developmental treatment with high-dose DBP improves spatial memory in male rats, and this effect may be related to an increase in BDNF expression in the hippocampus in a p-CREB independent route.