Differential stimulation of neurotrophin release by the biocompatible nano-material (carbon nanotube) in primary cultured neurons

Abstract

In order to develop novel, effective therapies for central nervous system regeneration, it is essential to better understand the role of neurotrophic factors and to design, accordingly, better artificial scaffolds to support both neurite outgrowth and synapse formation. Both nerve growth factor and brain-derived neurotrophic factor are major factors in neural survival, development, synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime candidate coating material for such neural cultures, carbon nanotubes offer unique structural, mechanical, and electrical properties. In this study, carbon nanotubes coated glass-coverslips were used as the matrix of a primary neural culture system used to investigate the effects of carbon nanotubes on neurite outgrowth and nerve growth factor/brain-derived neurotrophic factor release and expression. For these purposes, we performed comparative analyses of primary cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated coverslips. The morphological findings showed definite carbon nanotubes effects on the neurite outgrowths and synaptogenic figures in both cortical and hippocampal neurons when compared with the non-coated negative control. Although the carbon nanotubes did not change neurotrophin expression levels, it stimulated brain-derived neurotrophic factor release into the media from both types of neurons. Accordingly, we suggest a different mechanism of action between carbon nanotubes and Matrigel in relation to the specific neurotrophic factors. Since carbon nanotubes supply long-term extracellular molecular cues for the survival and neurite outgrowths of cultured neurons, the results from this study will contribute to an understanding of carbon nanotubes biological effects and provide new insight into their role in the secretion of neurotrophic factors.

Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells

“…Kim et al . reported in 2014 that neurons cultivated on CNT-coated surfaces initiate their neurite outgrowth one to two days later than on standard coatings [ 16 ].…”

“…However, CNTs have been shown in some studies to serve as an extracellular matrix for neurons and to direct neurite outgrowth, regulate neurite branching as well as to provide adhesion points for neurons [ 15 ]. This makes CNTs a promising matrix for primary neuronal cell cultures [ 16 ] as an alternative to other established matrices (e.g. matrigel, laminin or poly-D/L-ornithine).…”

“…matrigel, laminin or poly-D/L-ornithine). Additionally, CNTs were able to influence the secretion of neuroprotective factors like brain-derived neurotrophic factor (BDNF) [ 16 ]. In the field of neuronal prostheses, CNT coatings could–apart from their excellent properties–provide a functionalization of the electrode surface which is favorable for neurons, possibly reducing foreign body reactions and immune response.…”

Neurobehavioral toxicity of carbon nanotubes in mice

“…exposure to CNTs, specially MWNTs. An in vitro investigation showed that CNTs did not change BDNF expression levels in primary cultured neurons on CNTs-coated coverslips but stimulated BDNF release into the media (Kim et al, 2008). Nowadays, CNTs are used as artificial scaffolds to support neurite outgrowth and synapse formation, but exact mechanisms underlying interactions of CNTs and neurotrophic factors as therapeutics in disorders of central nervous system are not well understood.…”

Carbon nanotube multilayered nanocomposites as multifunctional substrates for actuating neuronal differentiation and functions of neural stem cells

“…CNT-layered substrates are biocompatible and efficient in inducing stem cells to differentiate specifically to neurons [17][18][19] , promoting neurite outgrowth 20 , and enhancing synaptogenesis [21][22][23] and consequential development of neuronal network 24,25 .…”