Carbon Nanotubes Prolong the Regulatory Action of Nerve Growth Factor on the Endocannabinoid Signaling



Hassanzadeh P^{1, 2} ; Arbabi E³ ; Rostami F³ Show Affiliations
Source: Physiology and Pharmacology Published:2015

Abstract

Introduction: Carbon nanotubes (CNTs) have shown enormous potential in neuroscience. Nerve growth factor (NGF)-CNTs complex promotes the neuronal growth, however, the underlying mechanism(s) have not been clearly identified. Based on the known interplay between NGF and the endocannabinoid system, involvement of 2-Arachidonoyl glycerol (2-AG) has been considered as one of the significant components of this mechanism. Materials and Methods: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs. MWCNTs were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Following three times daily intracerebroventricular injections of NGF solution (2, 5, and 10 μg), and 5, 10, and 20 μg of acid- or amine-modified MWCNTs, or MWCNTs-NGF complex for either one or 7 days, 2-AG contents were quantified in the frontal cortex and hippocampus by isotope-dilution liquid chromatography/mass spectrometry. Results: FTIR confirmed the amino-functionalization of COOH-MWCNTs and NGF immobilization on the aminated MWCNTs. Chronic, but not acute, administration of MWCNTs-NGF complex and NGF solution at the highest dose tested led to the elevation of 2-AG at 1 h from the last injection (P<0.01 and P<0.001). 2-AG enhancement induced by MWCNTs-NGF complex lasted for up to 5 and 12 h post-injection (P<0.01 and P<0.001). 2-AG contents remained at the baseline level in the sham and groups receiving vehicle, acid- or amine-modified MWCNTs (P>0.05). Conclusion: Functionalized MWCNTs-NGF complex induces a long-lasting increase of brain 2-AG content indicating the efficiency of this nanostructure to provide a sustained concentration of NGF. Implication of 2-AG in the mechanism of action of NGF might be of great therapeutic significance in neurological disorders. © 2015, Iranian Society of Physiology and Pharmacology. All rights reserved.