Abstract：
Ferric-tannic nanoparticles (FTs) are now considered to be new pharmaceuticals appropriate for the prevention of brain aging and related diseases. We have previously shown that FTs could activate axon guidance pathways and cellular clearance functioning in neuronal cell lines. Herein, we further investigated whether FTs could activate the two coordinated neuronal functions of axon guidance and synaptic function in rat brains and neuronal cell lines. A single intravenous injection of a safe dose of FTs has been shown to activate a protein expression of axon attractant Netrin-1 and neurotransmitter receptor GABRA4 in the cerebral cortexes of male Wistar rats. According to RNA-seq with targeted analysis, axon guidance and synapses have been enriched and Ephrin membered genes have been identified as coordinating a network of genes for such processes. In vitro, as expected, FTs are also found to activate axon guidance markers and promote neuronal tubes in neuronal cell lines. At the same time, pre-synaptic markers (synaptophysin), post-synaptic markers (synapsin), and GABRA4 neurotransmitter receptors have been found to be activated by FTs. Interestingly, synaptophysin has been found to localize along the promoted neuronal tubes, suggesting that enhanced axon guidance is associated with the formation and transportation of pre-synaptic vesicles. Preliminarily, repeated injection of FTs into adult rats every 3 days for 10 times could enhance an expression of synaptophysin in the cerebral cortex, as compared to control rats. This work demonstrates that FTs can be used for activating brain function associated with axon guidance and synaptic function.
摘要：
铁单宁纳米颗粒（FTs）现在被认为是适用于预防大脑衰老和相关疾病的新药。我们先前已经表明，FTs可以激活神经元细胞系中的轴突引导途径和细胞清除功能。在这里，我们进一步研究了FTs是否可以激活大鼠大脑和神经元细胞系中轴突引导和突触功能这两种协调的神经元功能。已证明单次静脉注射安全剂量的FTs可激活雄性Wistar大鼠大脑皮层中轴突引诱剂Netrin-1和神经递质受体GABRA4的蛋白表达。根据具有靶向分析的RNA-seq，轴突指导和突触已被丰富，Ephrin元基因已被鉴定为协调此类过程的基因网络。体外，正如预期的那样，还发现FT激活轴突导向标记并促进神经元细胞系中的神经元管。同时,突触前标记（突触素），突触后标记（突触素），发现GABRA4神经递质受体被FTs激活。有趣的是,已经发现突触素沿着促进的神经元管定位，提示轴突导向增强与突触前囊泡的形成和运输有关。初步而言,成年大鼠每3天重复注射FTs10次可增强大脑皮质突触素的表达,与对照大鼠相比。这项工作表明，FT可用于激活与轴突引导和突触功能相关的大脑功能。
