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.

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.

Gold nanoparticles produce transient reactive gliosis in the adult brain.

Gold nanoparticles (GNPs) have unique physical and chemical properties that allow them to function as a drug-delivery system for several tissues: skin, eye, liver, and others. However, information about the biological response of brain tissue against GNPs is limited. Astrocytes and microglia cells are the first line of defense against brain insults and proper indicators of the level of brain damage. This study was aimed to evaluate the astrocytic and microglia response after an intracerebral injection of polyethylene-glycol-coupled GNPs (PEGylated GNPs). We injected spherical PEGylated GNPs (85 × 106 nanoparticles /nl) with a glass micropipette (inner diameter =35 µm) into the striatum of P60 CD1 mice. We evaluated the cellular response of astrocytes and microglia on days 3, 7, 14, 30, and 90 after intracerebral injection. For both astrocytes and microglia cells, our findings indicated that the glial response was transient and mainly circumscribed to the injection site. This evidence suggests that PEGylated GNPs are well-tolerated by the neural tissue. Understanding the effects of GNPs in the adult brain is a crucial step to design proper pharmacological vehicles to deliver long-lasting drugs.

Emerging roles of microglia cells in the regulation of adult neural stem cells.

Microglia cells were first described as a component for the brain with few beneficial functions. The classical point of view implied that these cells had inflammatory properties more than benefits for brain homeostasis. To date, this assumption has changed and new roles of microglia cells are continuously discovered. Although, the main function of microglia cells is to provide a cellular defense against harmful or pathogen agents (bacteria, viruses, fungi, toxins, etc.), recent evidence indicates that microglial cells are dynamic modulators of synaptic pruning, brain development and neurogenesis by maintaining a balance of local cell population. In this commentary, we summarized the emerging role of the relationship between microglia cells and the neural stem cells resident in the ventricular-subventricular zone (V-SVZ), the largest neurogenic niche in the adult brain.