Viral mouse models used to study multiple sclerosis: past and present

Libbey, Jane E.; Fujinami, Robert S.

doi:10.1007/s00705-021-04968-5

Cited by 16 publications

(22 citation statements)

References 209 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Theiler's murine encephalomyelitis virus (TMEV) is a naturally occurring neurotropic, single-stranded RNA murine virus, often used to model human neurological damage associated with viral infections, e.g., epilepsy and MS [20,21]. While studies in inbred 2 of 22 mouse models have established different pathologies after TMEV infection, including seizures and demyelinating disease [22,23], a consistent finding is the variability of immune responses detected among infected models [24,25].…”

Section: Introductionmentioning

confidence: 99%

Serum Cytokines Predict Neurological Damage in Genetically Diverse Mouse Models

Gómez

Karmakar

Carroll

et al. 2022

Cells

View full text Add to dashboard Cite

Viral infections contribute to neurological and immunological dysfunction driven by complex genetic networks. Theiler’s murine encephalomyelitis virus (TMEV) causes neurological dysfunction in mice and can model human outcomes to viral infections. Here, we used genetically distinct mice from five Collaborative Cross mouse strains and C57BL/6J to demonstrate how TMEV-induced immune responses in serum may predict neurological outcomes in acute infection. To test the hypothesis that serum cytokine levels can provide biomarkers for phenotypic outcomes of acute disease, we compared cytokine levels at pre-injection, 4 days post-injection (d.p.i.), and 14 d.p.i. Each strain produced unique baseline cytokine levels and had distinct immune responses to the injection procedure itself. Thus, we eliminated the baseline responses to the injection procedure itself and identified cytokines and chemokines induced specifically by TMEV infection. Then, we identified strain-specific longitudinal cytokine profiles in serum during acute disease. Using stepwise regression analysis, we identified serum immune markers predictive for TMEV-induced neurological phenotypes of the acute phase, e.g., IL-9 for limb paralysis; and TNF-α, IL-1β, and MIP-1β for limb weakness. These findings indicate how temporal differences in immune responses are influenced by host genetic background and demonstrate the potential of serum biomarkers to track the neurological effects of viral infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Serum Cytokines Predict Neurological Damage in Genetically Diverse Mouse Models

Gómez

Karmakar

Carroll

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…He also described that the mouse virus is very rarely present in the CNS of normal mice but that intracerebral inoculation of mice with filtrates prepared from the intestinal contents of normal mice induced encephalomyelitis and the associated neurological phenotype ( Theiler and Gard, 1940b ). Due to the development of chronic inflammatory demyelinating disease in susceptible mouse strains such as SJL, intracerebral infection of such mice with the Daniels (DA) or BeAn 8386 (BeAn) strains of TMEV has been used as an animal model for MS for approximately the past 50 years ( Libbey and Fujinami, 2021 ; Figure 6A ). The T cell-mediated autoimmune demyelinating disease in SJL mice is characterized by weakness of the hind limbs, which advances to severe spastic paralysis, and inflammatory demyelination in the spinal cord.…”

Section: The Theiler’s Murine Encephalomyelitis Virus Mouse Model To ...mentioning

confidence: 99%

Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

Löscher

Howe

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Seizures are a common presenting symptom during viral infections of the central nervous system (CNS) and can occur during the initial phase of infection (“early” or acute symptomatic seizures), after recovery (“late” or spontaneous seizures, indicating the development of acquired epilepsy), or both. The development of acute and delayed seizures may have shared as well as unique pathogenic mechanisms and prognostic implications. Based on an extensive review of the literature, we present an overview of viruses that are associated with early and late seizures in humans. We then describe potential pathophysiologic mechanisms underlying ictogenesis and epileptogenesis, including routes of neuroinvasion, viral control and clearance, systemic inflammation, alterations of the blood-brain barrier, neuroinflammation, and inflammation-induced molecular reorganization of synapses and neural circuits. We provide clinical and animal model findings to highlight commonalities and differences in these processes across various neurotropic or neuropathogenic viruses, including herpesviruses, SARS-CoV-2, flaviviruses, and picornaviruses. In addition, we extensively review the literature regarding Theiler’s murine encephalomyelitis virus (TMEV). This picornavirus, although not pathogenic for humans, is possibly the best-characterized model for understanding the molecular mechanisms that drive seizures, epilepsy, and hippocampal damage during viral infection. An enhanced understanding of these mechanisms derived from the TMEV model may lead to novel therapeutic interventions that interfere with ictogenesis and epileptogenesis, even within non-infectious contexts.

show abstract

“…The mechanism by which milk could trigger autoimmunity through a response to CNS antigens, contributing to the development of MS, is not fully clarified, but high cell reactivity has been reported against several cow's milk proteins in MS patients [63]. Another milk protein involved in molecular mimicry is butyrophilin (BTN) [64]. [65].…”

Section: Milk Dairy Products and Msmentioning

confidence: 99%

Involvement of the Intestinal Microbiota in the Appearance of Multiple Sclerosis: Aloe vera and Citrus bergamia as Potential Candidates for Intestinal Health

et al. 2022

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a neurological and inflammatory autoimmune disease of the Central Nervous System in which selective activation of T and B lymphocytes prompts a reaction against myelin, inducing demyelination and axonal loss. Although MS is recognized to be an autoimmune pathology, the specific causes are many; thus, to date, it has been considered a disorder resulting from environmental factors in genetically susceptible individuals. Among the environmental factors hypothetically involved in MS, nutrition seems to be well related, although the role of nutritional factors is still unclear. The gut of mammals is home to a bacterial community of about 2000 species known as the “microbiota”, whose composition changes throughout the life of each individual. There are five bacterial phylas that make up the microbiota in healthy adults: Firmicutes (79.4%), Bacteroidetes (16.9%), Actinobacteria (2.5%), Proteobacteria (1%) and Verrucomicrobia (0.1%). The diversity and abundance of microbial populations justifies a condition known as eubiosis. On the contrary, the state of dysbiosis refers to altered diversity and abundance of the microbiota. Many studies carried out in the last few years have demonstrated that there is a relationship between the intestinal microflora and the progression of multiple sclerosis. This correlation was also demonstrated by the discovery that patients with MS, treated with specific prebiotics and probiotics, have greatly increased bacterial diversity in the intestinal microbiota, which might be otherwise reduced or absent. In particular, natural extracts of Aloe vera and bergamot fruits, rich in polyphenols and with a high percentage of polysaccharides (mostly found in indigestible and fermentable fibers), appear to be potential candidates to re-equilibrate the gut microbiota in MS patients. The present review article aims to assess the pathophysiological mechanisms that reveal the role of the microbiota in the development of MS. In addition, the potential for supplementing patients undergoing early stages of MS with Aloe vera as well as bergamot fibers, on top of conventional drug treatments, is discussed.

show abstract

Viral mouse models used to study multiple sclerosis: past and present

Cited by 16 publications

References 209 publications

Serum Cytokines Predict Neurological Damage in Genetically Diverse Mouse Models

Serum Cytokines Predict Neurological Damage in Genetically Diverse Mouse Models

Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

Involvement of the Intestinal Microbiota in the Appearance of Multiple Sclerosis: Aloe vera and Citrus bergamia as Potential Candidates for Intestinal Health

Contact Info

Product

Resources

About