EGF-Coupled Gold Nanoparticles Increase the Expression of CNPase and the Myelin-Associated Proteins MAG, MOG, and MBP in the Septal Nucleus Demyelinated by Cuprizone

Abstract

Current pharmacological therapies against demyelinating diseases are not quite satisfactory to promote remyelination. Epidermal growth factor (EGF) can expand the population of oligodendrocyte precursor cells (OPCs) that may help with the remyelination process, but its delivery into the injured tissue is still a biomedical challenge. Gold nanoparticles (GNPs) may be a useful tool for drug delivery into the brain. To evaluate remyelination in the septal nucleus, we administered intracerebral GNPs coupled with EGF (EGF–GNPs). C57BL6/J mice were demyelinated with 0.4% cuprizone (CPZ) and divided into several groups: Sham, Ctrl, GNPs, EGF, and EGF–GNPs. We evaluated the remyelination process at two time-points: 2 weeks and 3 weeks post-injection (WPI) of each treatment. We used the rotarod for evaluating motor coordination. Then, we did a Western blot analysis myelin-associated proteins: CNPase, MAG, MOG, and MBP. EGF–GNPs increase the expression of CNPase, MAG, and MOG at 2 WPI. At 3 WPI, we found that the EGF–GNPs treatment improves motor coordination and increases MAG, MOG, and MBP. EGF–GNPs enhance the expression of myelin-associated proteins and improve the motor coordination in mice. Thus, EGF-associated GNPs may be a promising pharmacological vehicle for delivering long-lasting drugs into the brain.

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

“…The latter results are remarkable as it has been demonstrated that after completed remyelination, axonal degeneration progresses at a low level, accumulating over time [ 117 ]. Notably, as some studies did not evaluate motor performance at the end of the cuprizone intoxication period [ 95 , 102 ], no conclusions can be drawn from these studies as to whether remyelination was paralleled by any functional recovery.…”