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Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis
1Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Abstract:
In this review, we compare and contrast two popular models for multiple sclerosis (MS), Theiler's murine encephalomyelitis virus (TMEV) disease and experimental allergic encephalomyelitis (EAE). These models are used to investigate the viral and autoimmune etiology of MS, respectively. Infection with live TMEV is an essential component of TMEV demyelinating disease. TMEV-specific cellular and humoral immunity and apoptosis of infected cells eliminate virus from the gray matter of the central nervous system (CNS) during the acute phase of TMEV disease. In contrast, during the chronic phase, TMEV persistently infects glial cells and/or macrophages in the white matter. During the chronic phase, recruitment of macrophages, TMEV-specific T cells and antibody, with the induction of apoptosis are harmful to the host, leading to inflammation and demyelination. In EAE, induction of encephalitogenic CD4+ T cells is an important component for disease. After stimulation and activation, these T cells upregulate adhesion molecules and are able to enter the CNS. Th1 cytokines augment the recruitment of mononuclear cells in the CNS. Macrophages and/or glial cells secrete cytotoxic factors leading to demyelination in conjunction with B cells secreting anti-myelin antibody. Although immunopathological pathways during the course of the demyelination in TMEV infection and EAE are not always the same, oligodendroglial apoptosis is observed in both models, suggesting that their demyelinating processes share a common terminal pathway and finally lead to quite a similar clinical and pathological picture.
Insights
This review compares Theiler's murine encephalomyelitis virus (TMEV) disease and experimental allergic encephalomyelitis (EAE) models for multiple sclerosis (MS). Both models show oligodendroglial apoptosis, indicating a shared pathway in demyelination.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Animal Models of Neurological Disorders
Background:
- Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS).
- Investigating the viral and autoimmune etiologies of MS is crucial for understanding disease pathogenesis.
- Theiler's murine encephalomyelitis virus (TMEV) disease and experimental allergic encephalomyelitis (EAE) are widely used animal models for MS research.
Purpose of the Study:
- To compare and contrast the TMEV disease and EAE models in the context of multiple sclerosis.
- To elucidate the distinct and shared immunopathological mechanisms underlying demyelination in these models.
- To highlight common terminal pathways leading to similar clinical and pathological outcomes in MS models.
Main Methods:
- Comparative review of existing literature on TMEV disease and EAE models.
- Analysis of viral-induced (TMEV) versus autoimmune-induced (EAE) demyelinating processes.
- Examination of cellular and humoral immune responses, cytokine profiles, and cell death mechanisms.
Main Results:
- TMEV disease involves acute viral clearance and chronic inflammation/demyelination driven by viral persistence and immune responses.
- EAE is characterized by autoimmune attack mediated by encephalitogenic T cells, leading to CNS inflammation and demyelination.
- Both models exhibit oligodendroglial apoptosis, suggesting a common final pathway in demyelination despite differing initial triggers.
Conclusions:
- TMEV and EAE models offer distinct yet complementary insights into MS pathogenesis.
- Shared mechanisms, particularly oligodendroglial apoptosis, underscore commonalities in the terminal stages of demyelination.
- Understanding these models aids in developing targeted therapies for multiple sclerosis.