Physiology and Pharmacology

en Carbon nanotubes prolong the regulatory action of nerve growth factor on the endocannabinoid signaling Nervous system (others) Others Experimental research article Experimental research article 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 remained elusive. Based on the interplay between NGF and the endocannabinoid system, involvement of the neuroprotective endocannabinoid, 2-arachidonoyl glycerol (2-AG), was investigated in the mechanism of action of NGF. 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). In vitro cytotoxicity was evaluated by MTT assay. Following three times daily intracerebroventricular injections of NGF solution (2, 5, and 10 &mug), and 5, 10, and 20 &mug 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 of rats by isotope-dilution liquid chromatography/mass spectrometry. Results: FTIR confirmed the amino-functionalization of COOH-MWCNTs and NGF immobilization on the aminated MWCNTs. Aminated MWCNTs and MWCNTs-NGF complex showed less cytotoxicity than COOH-MWCNTs (P<0.05, P<0.01, and P<0.01). 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 the neurological disorders. Carbon nanotubes, Nerve growth factor, Endocannabinoid signaling 167 176 http://ppj.phypha.ir/browse.php?a_code=A-10-858-2&slc_lang=en&sid=1 Parichehr Hassanzadeh hassanzadehparichehr4@gmail.com 3200319475328460015865 3200319475328460015865 Yes Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Elham Arbabi arbabiavalelham@gmail.com 3200319475328460015866 3200319475328460015866 No Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Rostami frostamii@yahoo.com 3200319475328460015867 3200319475328460015867 No Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Atyabi 3200319475328460015868 3200319475328460015868 No Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Rassoul Dinarvand 3200319475328460015869 3200319475328460015869 No Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran