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.
Keywords: Demyelination, EAE, MHV, Multiple sclerosis, Neurodegeneration,
Neuroinflammation, TMEV
