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Role of nuclear factor ?B in multiple sclerosis and experimental autoimmune encephalomyelitis.

ABSTRACT: The transcription factor nuclear factor ?B (NF-?B) plays major roles in inflammatory diseases through regulation of inflammation and cell viability. Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). It has been shown that NF-?B is activated in multiple cell types in the CNS of MS patients, including T cells, microglia/macrophages, astrocytes, oligodendrocytes, and neurons. Interestingly, data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis, have suggested that NF-?B activation in these individual cell types has distinct effects on the development of MS. In this review, we will cover the current literature on NF-?B and the evidence for its role in the development of MS and its animal model experimental autoimmune encephalomyelitis.

SUBMITTER: Yue Y

PROVIDER: S-EPMC6126134 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Role of nuclear factor κB in multiple sclerosis and experimental autoimmune encephalomyelitis.

Yue Yuan Y Stone Sarrabeth S Lin Wensheng W

Neural regeneration research 20180901 9

The transcription factor nuclear factor κB (NF-κB) plays major roles in inflammatory diseases through regulation of inflammation and cell viability. Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). It has been shown that NF-κB is activated in multiple cell types in the CNS of MS patients, including T cells, microglia/macrophages, astrocytes, oligodendrocytes, and neurons. Interestingly, data from animal model studi ...[more]

PMID: 30127103

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Project description:Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that involves the autoreactive T-cell attack on axonal myelin sheath. Lesions or plaques formed as a result of repeated damage and repair mechanisms lead to impaired relay of electrical impulses along the nerve, manifesting as clinical symptoms of MS. Evidence from studies in experimental autoimmune encephalomyelitis (EAE) models of MS strongly suggests that mitochondrial dysfunction presents at the onset of disease and throughout the disease course. The aim of this study was to determine if mitochondrial dysfunction occurs before clinical symptoms arise, and whether this is confined to the CNS. EAE was induced in C57B/L6 mice, and citrate synthase and mitochondrial respiratory chain (MRC) complex I-IV activities were assayed at presymptomatic (3 or 10 days post first immunisation (3 or 10 DPI)) and asymptomatic (17 days post first immunisation (17 DPI) time-points in central nervous system (CNS; spinal cord) and peripheral (liver and jaw muscle) tissues. Samples from animals immunised with myelin oligodendrocyte glycoprotein (MOG) as EAE models were compared with control animals immunised with adjuvant (ADJ) only. Significant changes in MOG compared to control ADJ animals in MRC complex I activity occurred only at presymptomatic stages, with an increase in the spinal cord at 10 DPI (87.9%), an increase at 3 DPI (25.6%) and decrease at 10 DPI (22.3%) in the jaw muscle, and an increase in the liver at 10 DPI (71.5%). MRC complex II/III activity changes occurred at presymptomatic and the asymptomatic stages of the disease, with a decrease occurring in the spinal cord at 3 DPI (87.6%) and an increase at 17 DPI (36.7%), increase in the jaw muscle at 10 DPI (25.4%), and an increase at 3 DPI (75.2%) and decrease at 17 DPI (95.7%) in the liver. Citrate synthase activity was also significantly decreased at 10 DPI (27.3%) in the liver. No significant changes were observed in complex IV across all three tissues assayed. Our findings reveal evidence that mitochondrial dysfunction is present at the asymptomatic stages in the EAE model of MS, and that the changes in MRC enzyme activities are tissue-specific and are not confined to the CNS.

Project description:Neuroinflammation is the coordinated response of the central nervous system (CNS) to threats to its integrity posed by a variety of conditions, including autoimmunity, pathogens and trauma. Activated astrocytes, in concert with other cellular elements of the CNS and immune system, are important players in the modulation of the neuroinflammatory response. During neurological disease, they produce and respond to cellular signals that often lead to dichotomous processes, which can promote further damage or contribute to repair. This occurs also in multiple sclerosis (MS), where astrocytes are now recognized as key components of its immunopathology. Evidence supporting this role has emerged not only from studies in MS patients, but also from animal models, among which the experimental autoimmune encephalomyelitis (EAE) model has proved especially instrumental. Based on this premise, the purpose of the present review is to summarize the current knowledge of astrocyte behavior in MS and EAE. Following a brief description of the pathological characteristics of the two diseases and the main functional roles of astrocytes in CNS physiology, we will delve into the specific responses of this cell population, analyzing MS and EAE in parallel. We will define the temporal and anatomical profile of astroglial activation, then focus on key processes they participate in. These include: (1) production and response to soluble mediators (e.g., cytokines and chemokines), (2) regulation of oxidative stress, and (3) maintenance of BBB integrity and function. Finally, we will review the state of the art on the available methods to measure astroglial activation in vivo in MS patients, and how this could be exploited to optimize diagnosis, prognosis and treatment decisions. Ultimately, we believe that integrating the knowledge obtained from studies in MS and EAE may help not only better understand the pathophysiology of MS, but also uncover new signals to be targeted for therapeutic intervention.

Dataset Information

Role of nuclear factor ?B in multiple sclerosis and experimental autoimmune encephalomyelitis.

Publications

Role of nuclear factor κB in multiple sclerosis and experimental autoimmune encephalomyelitis.

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