Printed Poster | Session 2

071 – Astrocyte disruption in EAE is associated with axonal injury and demyelination

Kevin Thorburn (1) – Jason Plemel (2) – Bradley Kerr (3)
University of Alberta, Pharmacology, Edmonton, Canada (1) – University of Alberta, Neurology, Edmonton, Canada (2) – University of Alberta, Anesthesiology and Pain Medicine, Edmonton, Canada (3)

Multiple Sclerosis (MS) is a central nervous system (CNS) disease characterized by inflammation, demyelination and axonal injury. In both MS and the animal model experimental autoimmune encephalomyelitis (EAE), astrocytes become activated and undergo molecular and morphological changes that can be beneficial or detrimental to CNS repair. In addition to becoming activated, astrocytes can be damaged during the course of MS and EAE. While significant progress has been made in understanding how activated astrocytes influence MS and EAE, relatively little is known about the role that injured astrocytes play in each disease. We have previously demonstrated that in mice with EAE there is a breakdown of the glia limitans that normally separates the peripheral and central nervous systems. Subsequent studies have revealed that in tissue sections with glia limitans disruption there is significantly greater T-cell infiltration, microglia/macrophage activation, demyelination and axonal injury. The increased immune cell infiltration and neural pathology can be detected in both male and female mice. However, female mice show significantly greater T-cell infiltration and axonal injury relative to males. In the tissue sections with disrupted glia limitans we also find that Iba-1 positive cells (i.e. macrophages and microglia) fill in areas devoid of astrocytes suggesting that macrophages and/or microglia create scar-like barriers similar to what has recently been described in spinal cord injury. We are currently carrying out experiments with the CX3CR1CreER mouse line to determine the relative contribution of each cell type to this scar-like barrier. We have also recently found that glial fibrillary acidic protein (GFAP) fragmentation, a marker of astrocyte injury, can be detected in the spinal cords of mice with EAE. Preliminary data suggests that there is significantly more GFAP fragmentation in animals at the peak of disease compared to animals at disease onset. Recently obtained in vitro data shows that myelin-reactivated T-cells are capable of killing astrocytes, as indicated by a reduction of GFAP staining. Current efforts are underway to characterize astrocyte function (e.g. phagocytosis) when cultured in the presence of autoreactive T-cells. Taken together, our data demonstrates that astrocyte injury in EAE is associated with more severe pathology and may be caused by infiltrating immune cells.