Nano-Based Tool for Promoting Neural Networks Activation
Growth factors fill an important role in neural development and therefore bestow great therapeutic potential for the treatment of neurodegenerative disease or injury. Specifically, the nerve growth factor NGF induces survival, maintenance and differentiation of neurons in the central and peripheral nervous system. In our study, we describe a new approach to promote neuronal differentiation and neurite outgrowth, by using a nano-based tool. We covalently conjugated NGF to iron oxide (γ-Fe2O3) nanoparticles, and tested the effect on NGFs' stability and bioactivity. For that purpose, we used PC12 cells which serve as a common model for neuronal differentiation. In response to NGF, PC12 cells differentiate into neuron-like cells, outgrow neurites and demonstrate electrical activity. We treated PC12 cells with NGF conjugated nanoparticles (NGF-NPs) at several concentrations and followed the neuronal differentiation process. We found that NGF-NPs treatment significantly promotes PC12 neurites outgrowth, compared to free NGF at the same concentration, and leads to an increase in the complexity of the branching trees. In addition, the examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. Next we investigated the role of the NP-based complex and the mechanism that led to promoted growth. We examined the effect of the NPs on the stability of the growth factor and the pathway through which the NP-NGF complex acts. We found that NGF-NPs induce cell differentiation via the regular TrkA pathway, as the conjugation to nanoparticles increases NGF availability by extending NGFs' half-life time. We conclude that there is an enhanced local availability of NGF at the vicinity of TrkA binding sites, leading to the promotion of the neuronal differentiation process. Our study demonstrates an effective nano-based complex, linking NGF to iron oxide nanoparticle, as a highly potentially tool for promoting neuronal differentiation and growth, contributing to the field of neuronal regeneration and repair.
* The research presented in the seminar was carried our towards the M.Sc. degree in Electrical Engineering, under the supervision of Dr. Orit Shefi