Enhanced axon guidance and synaptic markers in rat brains using ferric–tannic nanoparticles

Abstract

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.