长期成年人接触双A会通过抑制多巴胺载体贩运导致行为变化
Yu Shi1, Xiaoye Feng1, Chang Y Chung2,3
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, People's Republic of China.
Scientific reports
|April 19, 2025
概括
双A (BPA) 暴露会破坏多巴胺转运体 (DAT) 贩运,导致表面DAT表达的减少. 这种分子变化是BPA诱导的过度活跃和改变小鼠和虫的奖励行为的基础.
科学领域:
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 早期接触双A (BPA) 与神经行为发育问题有关.
- 乙对多巴胺水平的影响表明,它可能对奖励和运动途径产生影响.
- 通过BPA影响神经行为的精确分子机制尚不清楚.
研究的目的:
- 为了研究二A (BPA) 暴露如何影响成年小鼠的行为.
- 阐明BPA诱导的神经行为变化背后的分子机制,重点关注多巴胺转运器 (DAT) 贩运.
- 在神经元模型中检查BPA对DAT表面表达的影响.
主要方法:
- 成年小鼠暴露于BPA以评估行为变化.
- 使用光显微镜可视化黄色光蛋白标记的DAT (YFP-DAT) 局部化.
- 进行了MPTP毒性和APP+吸收试验,以评估DAT表面表达.
- 免疫光染色用于小鼠黑色物质 (SN) 神经元.
- 在体内研究中使用了表达GFP标记的DAT-1的Caenorhabditis elegans (C. elegans).
主要成果:
- 在成年小鼠中,BPA暴露引起过度活跃和异常的奖励反.
- BPA处理导致YFP-DAT在周核区域积聚,这表明贩运受损.
- 在BPA治疗细胞和小鼠SN神经元中,表面DAT表达减少.
- BPA对C. elegans的运动表现出双相作用,在50μM时增加身体曲,在100μM时减少.
结论:
- 暴露于BPA会破坏多巴胺转运体 (DAT) 的运输,并减少其在神经元中的表面表达.
- 受到影响的DAT流通和BPA表面表达有助于改变神经行为,包括过度活跃和奖励处理.
- 这些发现突出了BPA对奖励和运动系统的神经毒性影响的分子机制.
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