Peripheral nerves directly mediate the transneuronal translocation of silver nanomaterials from the gut to central nervous system

The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated nanoparticle translocation between organs is poorly understood. Here, we show that peripheral nerve fibers act as direct conduits for silver nanomaterials (Ag NMs) translocation from the gut to the CNS in both mice and rhesus monkeys. After oral gavage, Ag NMs are significantly enriched in the brain and spinal cord of mice with particle state, however do not efficiently enter the blood. Using truncal vagotomy and selective posterior rhizotomy, we unravel that the vagus and spinal nerves mediate the transneuronal translocation of Ag NMs from the gut to the brain and spinal cord, respectively. Single-cell mass cytometry analysis revealed that enterocytes and enteric nerve cells take up significant levels of Ag NMs for subsequent transfer to the connected peripheral nerves. Our findings demonstrate nanoparticle transfer along a previously undocumented gut-CNS axis mediated by peripheral nerves

既往研究认为，口服纳米颗粒进入中枢神经系统（central nervous system，CNS）的唯一途径为血液循环，而器官间非血液途径介导的纳米颗粒转位机制尚未得到充分阐释。本研究证实，外周神经纤维可作为银纳米材料（silver nanomaterials，Ag NMs）从肠道向中枢神经系统转位的直接通路，该现象在小鼠与恒河猴中均存在。经灌胃（oral gavage）给药后，银纳米材料以颗粒状态在小鼠脑与脊髓中显著富集，却无法有效进入血液循环。通过躯干迷走神经切断术（truncal vagotomy）与选择性脊神经后根切断术（selective posterior rhizotomy），本研究明确：迷走神经与脊神经分别介导银纳米材料经跨神经元转位从肠道抵达脑与脊髓。单细胞质谱流式细胞术（single-cell mass cytometry）分析显示，肠上皮细胞（enterocytes）与肠神经细胞（enteric nerve cells）可摄取大量银纳米材料，随后将其转运至相连的外周神经。本研究结果表明，纳米颗粒可沿着一条此前未被记载的、由外周神经介导的肠道-中枢神经系统轴通路实现跨器官转运。