pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis.

Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus [MSRV]-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.

Synthesis and Thermal Stability of Nanocrystalline Tetragonal Zirconia by Hydrolysis with Ethylene Diamine.

Nanocrystalline zirconia with high surface area and pure tetragonal crystalline phase was prepared using ethylene diamine (EDA), which acts as both precipitating agent and dispersant of the zirconium precursor. The yttria stabilized zirconia (Y-TZP) is a very attractive material due to its excellent biocompatibility, high fracture toughness, high strength and low wear rates. So zirconyl chloride octahydrate (ZrOCl2 · 8H2O) and yttrium chloride hexahydrate (YCl3 · 6H2O) in different molar ratios were used as starting solution. The detailed effects of various process parameters such as reaction time, concentration of the precursor solution, amount of ethylene diamine, and calcination temperature on the structural properties of the zirconia powders were investigated. The preparation conditions significantly affected the structural stability, crystal size, and crystal phase of the final material. Increases in the reaction time and amount of ethylene diamine led to a substantial increase of the crystal growth rate, the specific surface area, and the tetragonal content of the zirconia.