Silver nanoparticles (AgNPs) are increasingly incorporated in consumer products to confer antibacterial properties. AgNPs are shed during everyday use of these products, resulting in ingestion or inhalation and bioaccumulation in tissues including the brain. While these low levels of AgNPs do not induce DNA fragmentation typical of apoptosis or necrosis, they do interfere with cytoskeletal structure and dynamics in cultured differentiating adult neural stem cells (NSCs). Moreover, these cells form f-actin inclusions in response to 1 μg/ml AgNPs. Here, we report that these cytoskeletal inclusions colocalize with aggregates of the signaling protein β-catenin, a modulator of cytoskeletal dynamics. Pharmacological alteration of β-catenin signaling reduced formation of f-actin inclusions. AgNP exposure also resulted in a reduction of neurite length in differentiating NSCs, which was mimicked by pharmacological activation of β-catenin signaling. Conversely, pharmacological inhibition of the Wnt/β-catenin signaling pathway resulted in increased neurite lengths in control cells, but did not reverse the neurite collapse induced by AgNP exposure. Substantial changes in neurite length, in response to low-level AgNP or pharmacological manipulation of β-catenin signaling, occurred within the first six hours of exposure and were most evident in cells differentiating towards neural-like morphologies. We conclude that low-level exposure to AgNP, such as that resulting from use of consumer products, may disrupt β-catenin signaling in neural cells in an indirect or non-additive manner. Exposure to AgNP shed from consumer products at levels currently considered safe, may therefore alter physiological function of neural cells. This is of concern particularly regarding children, whose brains contain many developing neurons, and who may face bioaccumulation of AgNP over decades of exposure.

中文翻译：

---

成人神经干细胞暴露于低水平的银纳米粒子后，β-catenin参与细胞骨架破坏。

银纳米颗粒（AgNPs）越来越多地掺入消费产品中以赋予抗菌性能。在日常使用这些产品时，AgNP会脱落，从而导致包括大脑在内的组织被摄入或吸入并发生生物蓄积。尽管这些低水平的AgNP不会诱导凋亡或坏死所特有的DNA片段化，但它们确实会干扰培养的分化成年神经干细胞（NSC）的细胞骨架结构和动力学。此外，这些细胞响应1μg/ ml AgNPs形成f-肌动蛋白内含物。在这里，我们报道这些细胞骨架内含物与信号蛋白β-catenin（细胞骨架动力学的调节剂）的聚集体共定位。β-catenin信号转导的药理学改变可减少f-actin内含物的形成。AgNP暴露还导致分化的NSC中神经突长度的减少，这可以通过药理作用激活β-catenin信号传导来模拟。相反，Wnt /β-catenin信号通路的药理学抑制作用导致对照细胞中神经突长度增加，但没有逆转AgNP暴露诱导的神经突塌陷。响应于低水平的AgNP或药理作用的β-catenin信号，神经突长度发生实质性变化，发生在暴露后的最初6小时内，并且在分化为神经样形态的细胞中最明显。我们得出的结论是，低水平暴露于AgNP（例如使用消费品所导致的暴露）可能以间接或非累加的方式破坏神经细胞中的β-catenin信号传导。从消费品中流出的AgNP的水平目前认为是安全的，因此可能会改变神经细胞的生理功能。对于儿童来说，这尤其令人担忧，他们的大脑包含许多发育中的神经元，并且可能在数十年的暴露中面临AgNP的生物蓄积。