Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK S7N 5E2, Canada.
Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK S7N 5E2, Canada.
Environ Pollut. 2020 Jun;261:114060. doi: 10.1016/j.envpol.2020.114060. Epub 2020 Jan 25.
Evidence is emerging that environmental exposure to bisphenol S (BPS), a substitute for bisphenol A (BPA), to humans and wildlife is on the rise. However, research on the neurobehavioral effects of this endocrine disruptive chemical is still in its infancy. In this study, we aimed to investigate the effects of long-term exposure to environmentally relevant concentrations of BPS on recognition memory and its mechanism(s) of action, especially focusing on the glutamatergic/ERK/CREB pathway in the brain. Adult female zebrafish were exposed to the vehicle, 17β-estradiol (E2, 1 μg/L), or BPS (1, 10 and 30 μg/L) for 120 days. Fish were then tested in the object recognition (OR), object placement (OP), and social recognition tasks (SR). Chronic exposure to E2 and 1 μg/L of BPS improved fish performance in OP task. This was associated with an up-regulation in the mRNA expression of several subtypes of metabotropic and ionotropic glutamate receptors, an increase in the phosphorylation levels of ERK1/2 and CREB, and an elevated transcript abundance of several immediate early genes involved in synaptic plasticity and memory formation. In contrast, the exposure to 10 and 30 μg/L of BPS attenuated fish performance in all recognition memory tasks. The impairment of these memory functions was associated with a marked down-regulation in the expression and activity of genes and proteins involved in glutamatergic/ERK/CREB signaling cascade. Collectively, our study demonstrated that the long-term exposure to BPS elicits hermetic effects on the recognition memory in zebrafish. Furthermore, the effect of BPS on the recognition memory seems to be mediated by the glutamatergic/ERK/CREB signaling pathway.
有证据表明，环境中双酚 S（BPS）的暴露水平正在上升，BPS 是双酚 A（BPA）的替代品，人类和野生动物均受到了 BPS 的环境暴露。然而，这种内分泌干扰化学物质的神经行为效应研究仍处于起步阶段。在这项研究中，我们旨在研究长期暴露于环境相关浓度的 BPS 对识别记忆及其作用机制的影响，特别是关注大脑中的谷氨酸能/ERK/CREB 途径。成年雌性斑马鱼被暴露于载体、17β-雌二醇（E2，1μg/L）或 BPS（1、10 和 30μg/L）中 120 天。然后，鱼类在物体识别（OR）、物体放置（OP）和社会识别任务（SR）中进行测试。慢性暴露于 E2 和 1μg/L 的 BPS 可改善鱼类在 OP 任务中的表现。这与几种代谢型和离子型谷氨酸受体的 mRNA 表达上调、ERK1/2 和 CREB 的磷酸化水平升高以及参与突触可塑性和记忆形成的几种即刻早期基因的转录丰度升高有关。相比之下，暴露于 10 和 30μg/L 的 BPS 会减弱鱼类在所有识别记忆任务中的表现。这些记忆功能的损伤与参与谷氨酸能/ERK/CREB 信号级联的基因和蛋白的表达和活性的明显下调有关。总的来说，我们的研究表明，长期暴露于 BPS 会对斑马鱼的识别记忆产生封闭效应。此外，BPS 对识别记忆的影响似乎是通过谷氨酸能/ERK/CREB 信号通路介导的。
