Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a phosphorus-based flame retardant common in consumer goods and baby products. Concerns have been raised about TDCPP exposure and neurodevelopmental toxicity. However, the mechanism and early response for TDCPP-induced neurotoxicity are poorly understood. This study investigates the role of microglia-mediated neuroinflammation in TDCPP-induced neurotoxicity in mice and primary cells. TDCPP was administered to C57BL/6 pups (0, 5, or 50 mg/kg/day) via an oral gavage from postnatal days 10-38 (28 days). The results showed that TDCPP exposure for 28 days altered the gene expression of neuronal markers Tubb3, Nefh, and Nes, and led to apoptosis in the hippocampus. The mRNA levels of pro-inflammatory factors Il-1β, Tnfα and Ccl2 dose dependently increased in the hippocampus at both 24 h and 28 days following exposure, accompanied by microglia activation characterized by an amoeboid-like phenotype. In in vitro studies using the primary microglia isolated from neonatal mice, exposure to TDCPP (0-100 μM) for 24 h resulted in cellular activation. It also increased the expression of genes responsible for inflammatory responses including surface markers and pro-inflammatory cytokines. These changes occurred in a dose-dependent fashion. Neurite outgrowth of primary mouse hippocampal neurons was inhibited by treatment with the conditioned medium harvested from microglia exposed to TDCPP. These results reveal that neonatal exposure to TDCPP induces neuronal damage through microglia-mediated inflammation. This provides insight into the mechanism of TDCPP's neurodevelopmental toxicity, and suggests that microglial cell is a sensitive responder for OPFRs exposure.

中文翻译：

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新生儿暴露于有机磷阻燃剂TDCPP在体内和体外通过小胶质细胞介导的炎症在小鼠海马中引起神经毒性。

磷酸三（1,3-二氯-2-丙基）酯（TDCPP）是消费品和婴儿产品中常见的磷基阻燃剂。人们对TDCPP暴露和神经发育毒性提出了担忧。但是，对TDCPP诱导的神经毒性的机制和早期反应知之甚少。这项研究调查了小胶质细胞介导的神经炎症在TDCPP诱导的小鼠和原代细胞神经毒性中的作用。从出生后第10-38天（28天）开始，通过口服管饲法将TDCPP给药至C57BL / 6幼崽（0、5或50 mg / kg /天）。结果表明，TDCPP暴露28天会改变神经元标记Tubb3，Nefh和Nes的基因表达，并导致海马细胞凋亡。促炎因子II-1β的mRNA水平，在暴露后24小时和28天，海马中的Tnfα和Ccl2剂量依赖性地增加，伴随着以胶质样表型为特征的小胶质细胞活化。在使用从新生小鼠中分离出的原发性小胶质细胞的体外研究中，暴露于TDCPP（0-100μM）24小时导致了细胞活化。它还增加了负责炎症反应的基因的表达，包括表面标志物和促炎细胞因子。这些变化以剂量依赖性方式发生。通过用从暴露于TDCPP的小胶质细胞收集的条件培养基进行处理，可以抑制原代小鼠海马神经元的神经突生长。这些结果表明，新生儿暴露于TDCPP会通过小胶质细胞介导的炎症诱导神经元损伤。这提供了对TDCPP机制的洞察力