Low-dose bisphenol A exposure impairs learning and memory ability with alterations of neuromorphology and neurotransmitters in rats

Abstract

To investigate the developmental neurotoxicity of environmental bisphenol A (BPA) exposure for infants and children, postnatal rats were used as the animal model and were divided into four groups. Then, they were treated with different concentrations of BPA (i.e., 0, 0.5, 50, or 5000 μg/kg·bw/day of BPA as the control, low-, medium- and high-exposed group) from postnatal days 7 to 21. Y-maze tests, Golgi-Cox assays and liquid chromatography-tandem mass spectrometry (LC/MS/MS) were performed to test the changes of learning and memory ability, hippocampal neuromorphology and neurotransmitter levels, respectively. The results showed that the BPA-exposed rats, especially the low- and high-exposed rats, needed more trials and longer times to qualify for the learned criterion than the control rats. Additionally, rats after low- or high-exposure to BPA exhibited decreased DG dendritic complexity and reduced CA1 and DG dendritic spine densities in the hippocampus. Low-dosage BPA treatment could significantly alter the neurotransmitter contents in the hippocampus. In male rats, the levels of glutamic acid (Glu) and acetylcholine increased, while the 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) levels decreased, which lead to an unbalanced Glu/GABA ratio. However, in female rats, only 5-HT levels decreased. In conclusion, postnatal exposure to BPA could sex- and dose-dependently disrupt dendritic development and neurotransmitter homeostasis in the rat hippocampus. The impaired spatial learning and memory ability of rats induced by low-dose BPA is associated with both disrupted dendritic development and neurotransmitter homeostasis in the hippocampus.

Keywords: Bisphenol A; Dendritic complexity; Learning and memory; Neurotransmitters; Postnatal exposure; Spine densities.