Changes in Nrf2 Expression in the Spinal Cord in Mouse Model of Experimental Autoimmune Encephalomyelitis

Abstract

In this study, we investigated the expression of nuclear factor erythroid-derived 2related factor 2 (Nrf2) in the spinal cord using an experimental autoimmune encephalomyelitis (EAE) model. MOG35-55 was injected into female mice to induce an autoimmune response. Clinical scoring and a behavioral rotarod test were conducted to assess the successful modeling of EAE. Animals were sacrificed 1, 2, and 3 weeks after immunization. Spinal cords were prepared for morphometry, immunohistochemistry, and western blotting. Multifocal demyelination was observed in the white matter. Nrf2 immuno-reactivity was detected in astrocytes and neurons in spinal cord. Nrf2 immuno-reactive neurons and astrocytes had increased by 2 weeks after immunization, and their up-regulation was maintained until 3 weeks after immunization. Additionally, time-dependent up-regulation of Nrf2 in the spinal cord was investigated by western blotting. The level of NAD(P)H quinine oxidoreductase-1 protein, an Nrf2 target gene, was not changed during week 1, but showed a significant decrease 2 and 3 weeks after immunization. Parallel to upregulated Nrf2, heme oxygenase-1, another target gene of Nrf2, was significantly augmented until 3 weeks after immunization. We conclude that Nrf2 expression in neurons is involved in an autoimmune attack in the spinal cord in an EAE model.