Traveled Distance Is a Sensitive and Accurate Marker of Motor Dysfunction in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is a common central nervous system disease associated with progressive physical impairment. To study the mechanisms of the disease, we used experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE is induced by myelin oligodendrocyte glycoprotein35–55 peptide, and the severity of paralysis in the disease is generally measured using the EAE score. Here, we compared EAE scores and traveled distance using the open-field test for an assessment of EAE progression. EAE scores were obtained with a 6-step observational scoring system for paralysis, and the traveled distance was obtained by automatic trajectory analysis of natural exploratory behaviors detected by a computer. The traveled distance of the EAE mice started to decrease significantly at day 7 of the EAE process, when the EAE score still did not reflect a change. Moreover, in the relationship between the traveled distance and paralysis as measured by the EAE score after day 14, there was a high coefficient of determination between the distance and the score. The results suggest that traveled distance is a sensitive marker of motor dysfunction in the early phases of EAE progression and that it reflects the degree of motor dysfunction after the onset of paralysis in EAE.

Download Full-text

Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

Neurotherapeutics ◽

10.1007/s13311-020-00958-8 ◽

2020 ◽

Author(s):

Vittoria Borgonetti ◽

Maria Domenica Sanna ◽

Laura Lucarini ◽

Nicoletta Galeotti

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Rna Binding ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Rna Binding Protein ◽

Motor Dysfunction ◽

Autoimmune Encephalomyelitis ◽

Activated Microglia ◽

Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood–brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.

Download Full-text

Multiple Sclerosis and Schizophrenia: A Case Report

Psychiatry in Medicine ◽

10.2190/xn8k-p8ex-6x73-fgqg ◽

1972 ◽

Vol 3 (3) ◽

pp. 251-257 ◽

Cited By ~ 8

Author(s):

Marc H. Hollender ◽

Philip P. Steckler

Keyword(s):

Multiple Sclerosis ◽

Psychiatric Disorder ◽

Central Nervous System Disease ◽

Dramatic Improvement ◽

Healthy Children ◽

System Disease ◽

Essential Questions ◽

Sodium Amobarbital ◽

Relationship Of ◽

The Relationship

In the borderland between psychiatry and neurology the clinician occasionally encounters patients with diseases which challenge diagnostic skills and treatment methods. A case is presented in which the coexistence of multiple sclerosis and schizophrenia raises essential questions about the relationship of mind and brain. A young woman with multiple sclerosis developed a clinical picture of schizophrenia in the initial stages of her disease. During sodium amobarbital interviews the patient's mental functioning cleared temporarily, although tranquilizers failed to control disruptive behavior. Electroconvulsive therapy was administered with dramatic improvement of her psychiatric disorder and no worsening of her neurological disease. In the seven years since recovery she has married and raised two healthy children without recurrence of either neurological or psychiatric disorder. While no cause-and-effect relationship can be defined, such cases emphasize the need for further studies of the relationship of central nervous system disease to psychiatric disorder.

Download Full-text

Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model

Beneficial Microbes ◽

10.3920/bm2017.0116 ◽

2018 ◽

Vol 9 (3) ◽

pp. 495-513 ◽

Cited By ~ 19

Author(s):

J.E. Libbey ◽

J.M. Sanchez ◽

D.J. Doty ◽

J.T. Sim ◽

M.F. Cusick ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Severity ◽

Tricarboxylic Acid Cycle ◽

Preclinical Model ◽

Autoimmune Encephalomyelitis ◽

Immune Mediated ◽

Genus Lactobacillus ◽

The Central Nervous System ◽

The Relationship ◽

Experimental Autoimmune

Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.

Download Full-text

Increased Post-Translational Lysine Acetylation of Myelin Basic Protein is Associated with Peak Neurological Disability in a Mouse Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

10.26226/morressier.59a3e8b5d462b8028d8947ee ◽

2017 ◽

Author(s):

Tina Khorshid Ahmad

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Myelin Basic Protein ◽

Basic Protein ◽

Lysine Acetylation ◽

Autoimmune Encephalomyelitis ◽

Neurological Disability ◽

Experimental Autoimmune Encephalomyelitis Model ◽

Mouse Experimental Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Download Full-text

Potential Role of Humoral Immunity in the Pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)

Frontiers in Bioscience ◽

10.2741/2268 ◽

2007 ◽

Vol 12 (1) ◽

pp. 2735 ◽

Cited By ~ 18

Author(s):

Maria del Pilar Martin

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Humoral Immunity ◽

Potential Role ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Download Full-text

Faculty Opinions recommendation of TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717964119.793477152 ◽

2013 ◽

Author(s):

Hugues Abriel

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Neuronal Degeneration ◽

Cation Channel ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Download Full-text

Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130252 ◽

2014 ◽

Vol 72 (2) ◽

pp. 152-156 ◽

Cited By ~ 5

Author(s):

Doralina Guimarães Brum ◽

Elizabeth Regina Comini-Frota ◽

Claúdia Cristina F. Vasconcelos ◽

Elza Dias-Tosta

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Vitamin D ◽

Environmental Factors ◽

Scientific Evidence ◽

Hypovitaminosis D ◽

Central Nervous System Disease ◽

Keywords Multiple Sclerosis ◽

System Disease ◽

Genetic And Environmental Factors

Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating, and degenerative central nervous system disease. Even though the etiology of MS has not yet been fully elucidated, there is evidence that genetic and environmental factors interact to cause the disease. Among the main environmental factors studied, those more likely associated with MS include certain viruses, smoking, and hypovitaminosis D. This review aimed to determine whether there is evidence to recommend the use of vitamin D as monotherapy or as adjunct therapy in patients with MS. We searched PUBMED, EMBASE, COCHRANNE, and LILACS databases for studies published until September 9 th , 2013, using the keywords “multiple sclerosis”, “vitamin D”, and “clinical trial”. There is no scientific evidence up to the production of this consensus for the use of vitamin D as monotherapy for MS in clinical practice.

Download Full-text