020 – Novel Mechanisms of Neurodegeneration in an Animal Model of Multiple Sclerosis

Printed Poster | Session 2

020 – Novel Mechanisms of Neurodegeneration in an Animal Model of Multiple Sclerosis

Cole Libner (1, 4, 5) – Hannah Salapa (2, 4, 5) – Michael Levin (2, 3, 4, 5)
Department of Health Sciences (1) – Department of Anatomy, Physiology and Pharmacology (2) – Department of Neurology (3) – Cameco Multiple Sclerosis Neuroscience Research Center (4) – Office of the SK MS Clinical Research Chair, University of Saskatchewan, Saskatoon, SK, Canada (5)


Background: Autoimmunity to the RNA binding protein heterogeneous nuclear ribonuclear protein A1 (A1) has been shown to contribute to the pathogenesis of neurodegeneration (NDG) in MS. Our lab was the first to show that neurons in the brain of a MS patient showed pathogenic features of A1 dysfunction. Using experimental autoimmune encephalomyelitis (EAE), injection of anti-A1 antibodies caused worse disease and increased NDG of the ventral spinocerebellar tract (VSCT). The mechanisms of the observed NDG are largely unknown.
Objectives: To examine mechanisms related to anti-A1 antibody mediated NDG in EAE, using the VSCT as a model. These experiments are important because current models of NDG are inadequate and NDG likely results in permanent disability in MS patients.
Methods: To identify VSCT neuronal cell bodies, mice were injected into the cerebellum with Fluorogold, a retrograde tracer. Following intracerebellar injections, EAE was induced by immunization with myelin oligodendrocyte glycoprotein, and mice were injected with anti-A1 or control antibodies. Brain and spinal cord were processed and analyzed by immunohistochemistry using three-dimensional microscopy.
Results: Following cerebellar injections and EAE, fluorogold was successfully localized to neuronal cell bodies of the VSCT in the ventral lumbosacral spinal cord. In contrast to mice injected with saline or isotype control IgG, anti-A1 antibody injected mice with EAE showed the following in the ventral lumbosacral spinal cord and accompanying VSCT neuronal cell bodies: 1. reduced numbers of neuronal cell bodies, 2. increased CD16 expression (FcRIII), 3. localization of anti-A1 antibodies in close proximity to CD16+ immune cells, and 4. localization of anti-A1 antibodies adjacent to, on and within neuronal cell bodies. Further, there was increased nitric oxide synthase within neuronal cell bodies as well as in surrounding tissue.
Conclusion: Considering that that EAE is an ascending paralysis that begins in the lumbosacral cord; the VSCT and its cell bodies can be used for studying the mechanisms related anti-A1 antibody mediated NDG in EAE, which has important implications for the pathogenesis of MS.