Numerous studies have suggested that nano-TiO₂ can be translocated to the brain via the placental barrier and blood brain barrier, leading to brain damage and cognitive impairment in both mice and rat offspring. The mechanism of nanoTiO₂-induced neurotoxicity is still unclear, as is its role in the inhibition of hippocampal development. In this experiment, nano-TiO₂ was employed to investigate whether the inhibition of the hippocampal development of mice offspring involved the alterations in the Rho signaling pathway following consecutive gavage of female mice between 7-21 days postpartum. The results showed that nano-TiO₂ particles were concentrated in the hippocampus of offspring, resulting in reduced hippocampal indices and in inhibited axonal and dendritic growth. Furthermore, nano-TiO₂ downregulated expression of N-methyl-D-aspartate receptor (NR)1, NR2A, NR2B, RhoGTPase, Ras-related C1 botulinum toxin substrate (Rac1), cell division cycle42 (Cdc42), phosphorylated cAMP response element binding protein (p-CREB), p21-activated kinase (PAK) 3, and PAK1, LIMK (LIM kinase) 1, p-LIMK1, activated Cdc42 kinase (ACK), and myotonic dystrophic kinaseassociated Cdc42-binding kinase (MRCK) and increased expression of RhoA, Rho kinase (ROCK) 1 and cyclin dependent kinase (Cdk) 5 in offspring. In addition, nano-TiO₂ disrupted the balance of RhoA/Rac1, RhoA/Cdc42, and Rac1/Cdc42 ratios in the hippocampus of mice offspring. Taken together, these data imply that maternal exposure to nano-TiO₂ inhibited development of hippocampal axons and dendrites of offspring may be correlated with the dysfunction of the Rho pathway and that N-methyl-D-aspartate receptors (NMDAR) may also mediate nano-TiO₂-Rho pathway interactions.

中文翻译：

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母体暴露于纳米二氧化钛会导致海马发育受到抑制，涉及到后代的Rho / NMDAR信号通路的功能障碍。

大量研究表明，纳米TiO 2可以通过胎盘屏障和血脑屏障转移到大脑，从而导致小鼠和大鼠后代的脑损伤和认知障碍。纳米TiO 2诱导的神经毒性的机制尚不清楚，其在抑制海马发育中的作用也不清楚。在该实验中，用纳米二氧化钛研究了对小鼠后代海马发育的抑制是否涉及在产后7-21天之间连续灌食雌性小鼠后Rho信号通路的改变。结果表明，纳米TiO 2颗粒集中在后代的海马中，导致海马指数降低，并抑制了轴突和树突的生长。此外，纳米TiO 2下调N-甲基-D-天冬氨酸受体（NR）1，NR2A，NR2B，RhoGTPase，与Ras相关的C1肉毒杆菌毒素底物（Rac1），细胞分裂周期42（Cdc42），磷酸化的cAMP反应元件结合蛋白的表达（ p-CREB），p21活化激酶（PAK）3和PAK1，LIMK（LIM激酶）1，p-LIMK1，活化Cdc42激酶（ACK）和强直性营养不良激酶相关的Cdc42结合激酶（MRCK）并增加了后代中的RhoA，Rho激酶（ROCK）1和细胞周期蛋白依赖性激酶（Cdk）5。另外，纳米二氧化钛破坏了小鼠后代海马中RhoA / Rac1，RhoA / Cdc42和Rac1 / Cdc42比例的平衡。在一起