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周产期暴露于免疫抑制剂di-n-octyltin二化物会影响大鼠的大脑发育

Didima M G de Groot¹, Louisa Linders¹, Reinier Kayser¹

¹Department of Toxicology and Applied Pharmacology, TNO Nutrition and Food Research (as part of TNO Quality of Life), Zeist, the Netherlands.

Toxicology mechanisms and methods

|November 10, 2023

概括

环境化学物质二-n-octyltin二化物 (DOTC) 破坏了老鼠的免疫和大脑发育. 这项研究将免疫毒性与神经发育影响联系起来,突出显示了免疫神经系统的联系.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
毒理学毒理学毒理学

背景情况:

环境化学物质可以破坏免疫系统的发展,可能导致神经发育障碍.
迪-n-octyltin二化物 (DOTC) 之前在老鼠中显示对母体和发育中的免疫系统有不良影响.
假设DOTC诱导的免疫毒性和神经发育影响之间的联系.

研究的目的:

研究DOTC暴露对大鼠结构和功能大脑发育的影响.
探索DOTC对免疫系统和神经发育的影响之间的联系.
利用先进的成像和基因组学来评估DOTC的神经发育毒性.

主要方法:

雄性大鼠 (F0代) 从交配前到F1后代牺牲时接受了DOTC (0,3,10,或30毫克/公斤饮食).
在体内MRI和[18F]FDG PET成像用于评估大脑结构和新陈代谢.
用行为测试,神经病理学和基因组学来评估神经发育和免疫学变化.

主要成果:

暴露于DOTC导致大脑区域 (MRI) 暂时扩大,并改变了特异性重量.
在大脑中观察到过渡性超新陈代谢 ([18F]FDG PET) 和听觉惊超响应.
基因组学揭示了关键神经发育,神经功能和免疫系统调节者的转录改变.

结论:

在成长中的老鼠中,DOTC暴露会影响大脑结构,功能和行为.
结果表明免疫毒性在DOTC诱导的神经系统损伤中起作用.
这项研究支持在大脑发育过程中免疫和神经系统之间存在很强的联系.

关键词:

神经发育神经发育大脑测量测量大脑测量这是一种di-n-octyltin二化物.扩展了一代生殖毒性研究.磁共振成像技术的使用微阵列是一个微阵列.神经毒性的作用.定子发射断层扫描 (PET).鼠标鼠标鼠标鼠标鼠标

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