Chapter 7

Advances in Experimental Animal Models Provide Insights into Different Etiology and Mechanism of Multiple Sclerosis to Design Therapeutics

Sourodip Sengupta and Jayasri Das Sarma*


Myelin covering of axons in the central and peripheral nervous system helps in faster propagation of neuronal action potentials. Demyelination is a neurodegenerative process in which the axons lose their myelin coverings, exposing the axons to surroundings and leading to a reduction in neuron-to-neuron communication. Several demyelinating diseases exist in humans, and one of the most frequently occurring demyelinating disease of the CNS is multiple sclerosis (MS). Although more than 2.3 million people suffer from MS globally, the disease etiology is still unknown, impeding the development of effective therapeutics. The available treatments are based on disease-modifying therapy to reduce or moderate the symptoms and slow the disease progression; however, none can cure the disease. One key to better design therapeutics is to understand the cellular and molecular mechanisms of MS by developing reliable model systems. Human studies have their own limitations, such as limited access to patient tissues. Moreover, genetic variability makes it difficult to identify the triggers of MS. This calls for the development of reliable experimental animal models to understand MS pathogenesis better. There is no exclusive experimental model that covers the entire gamut of the disease. In this chapter, we will discuss experiment autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus (TMEV), and mouse hepatitis virus (MHV)-induced models of demyelination that mimic specific histopathological and neurobiological aspects of multiple sclerosis. The present understanding of MS as an autoimmune disease mediated by self-reactive T-cells comes mainly from studies on the EAE model. Further, viral-induced demyelination models have provided valuable insights into a better understanding of MS. Studies in the TMEV model have demonstrated molecular mimicry and epitope spreading as major mechanisms of virus-induced neuroinflammation. Our knowledge of immune-mediated CNS damage has been further enhanced by studies on MHV-induced neuroinflammatory demyelination, suggesting macrophage-mediated myelin stripping in neurodegeneration. While the limitations of these models of MS are obvious, appropriate use of this model has led to the development of clinically useful drugs for the treatment of this devastating disease.

Total Pages: 139-159 (21)

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