Animal models of multiple sclerosis: From rodents to zebrafish

Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system. Animal models of MS have been critical for elucidating MS pathological mechanisms and how they may be targeted for therapeutic intervention. Here we review the most commonly used animal models of MS. Although these animal models cannot fully replicate the MS disease course, a number of models have been developed to recapitulate certain stages. Experimental autoimmune encephalomyelitis (EAE) has been used to explore neuroinflammatory mechanisms and toxin-induced demyelinating models to further our understanding of oligodendrocyte biology, demyelination and remyelination. Zebrafish models of MS are emerging as a useful research tool to validate potential therapeutic candidates due to their rapid development and amenability to genetic manipulation.

The role of chemokines and chemokine receptors in multiple sclerosis

“…In DA (Dark Agouti) rats, recombinant rat MOG can be used to induce EAE, which is characterized by demyelinating and spinal cord injury with subcutaneous and perivascular inflammatory infiltration [25]. In SJL/J mice, PLP 139-151 induced disease mimicking relapsing-remitting EAE [21,25]. MBP can induce acute self-limiting or chronic recurrent disease / progressive disease in guinea pigs.…”

Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals

“…Given the heightened significance of LDE-related electrophilic drugs, the ability to precisely perturb and probe LDE-associated stress response mechanisms and players that support these subcellular activities will be a major step forward toward understanding how context-dependent deregulation occurs in aging (Castelli et al, 2019) and in MS. For instance, G-REX targeted to particular subcellular locales in neurons can profile first-responder proteins to localized LDE generation. Although the compatibility of REX technologies with complex vertebrate animals such as larval zebrafish is encouraging , zebrafish MS models are still in their infancy (Burrows et al, 2019). Future tool development and effort should thus focus on multidiscplinary approaches such that LDE signaling can be studied in the most biomedically relevant context.…”

Biological models in multiple sclerosis

“…Zebrafish (Danio rerio) has been extensively used in developmental studies and in the last years because of its short lifecycle, physiological characteristics (Simons & Lyons, 2013), responsiveness to genetic manipulation, and a myelination process comparable to mammals (Buckley, Goldsmith, & Franklin, 2008), this organism has emerged as a promising model for the study of autoimmune demyelination and neurodegeneration (Burrows et al, 2019;Fang et al, 2015;Münzel, Becker, Becker, & Williams, 2014). In fact, zebrafish contains mammalian homologous genes involved in the myelination process (Dubois-Dalcq et al, 2008;Kim et al, 2011); nevertheless, immune system differences between zebrafish and mammals should be considered in the design and implementation of zebrafish immune-mediated human disease models.…”

“…In this model, toxin-induced demyelination and genetic cell ablation are commonly used to study the mechanisms regarding remyelination and OPCs differentiation. Zebrafish lysolecithin-induced demyelination shows OLs-specific toxicity with no evidence of a decrease in the number of axons and is considered a promising alternative for investigating remyelination mechanisms in a noninflammatory environment (Burrows et al, 2019). In remyelination therapeutics screening studies, genetic demyelination can be generated by the ablation of OLs (Chung et al, 2013).…”

“…EAE is the most widely used MS preclinical research immune-mediated in vivo experimental model (Burrows et al, 2019;García-Díaz & Estivill-Torrús, 2008). This is due to the high similarity between the model and the disease in humans.…”