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在不同妊娠阶段暴露于双氨酸对神经发育的影响

Chuchu Xi¹, Xiaoqian Shi¹, Yujing Wang¹

¹Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.

Ecotoxicology and environmental safety

|August 19, 2023

概括

晚期孕期暴露于双氨酸 (BF) 会导致小鼠的暂时神经发育缺陷. 怀孕后期的窗口最容易受到影响,与神经元传播和炎症的改变有关.

科学领域:

环境毒理学环境毒理学
神经科学是一个神经科学.
发育生物学是发展生物学.

背景情况:

已知围产期暴露于双氨酸 (BF) 会影响神经发育.
对于BF的神经毒性作用和潜在机制的关键发育窗口仍然不清楚.

研究的目的:

为了确定最容易受到BF诱导的神经发育变化的妊娠期.
研究在敏感的产前阶段与BF暴露相关的分子机制.

主要方法:

怀孕的小鼠在不同的妊娠期 (GD 0-5,6-15,16出生) 暴露于BF (0.5 mg/kg/d).
评估后代的神经行为缺陷,包括运动活动和学习/记忆.
分析了海马中的神经元损失和蛋白质/基因表达水平 (NMDA受体,炎症标志物).

主要成果:

在妊娠日 (GD) 16至出生 (B) 期间的暴露,在6周大时显著损害了后代的运动活动和学习/记忆.
这种晚期暴露还导致海马神经元损失,并改变了关键突触蛋白 (VGluT1,NR1,NR2A,NR2B,VGAT1) 和炎症基因 (Il-1β,Il-6,Tnf-α) 的表达.
在10周大的后代中没有观察到神经行为和病理缺陷,这表明依赖年龄的恢复.

结论:

怀孕后期 (GD 16-B) 是低剂量BF暴露的最脆弱时期,导致暂时的神经发育缺陷.
机制可能包括刺激/抑制平衡的破坏,NMDA受体功能的改变和神经炎症的增加.
这些发现突出了怀孕期间环境风险评估的关键窗口.

关键词:

双氨酸是双氨酸中的一种.孕期暴露孕期暴露学习和记忆的学习和记忆运动机动活动运动机动活动神经发育缺陷的神经发育缺陷

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