Dysfunctional RNA‐binding protein biology and neurodegeneration in experimental autoimmune encephalomyelitis in female mice

2019 ◽  
Vol 98 (4) ◽  
pp. 704-717 ◽  
Author(s):  
Hannah E. Salapa ◽  
Cole D. Libner ◽  
Michael C. Levin
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Autoimmune Encephalomyelitis ◽  
Female Mice ◽  
Experimental Autoimmune

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

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.

scholarly journals Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

2001 ◽  
Vol 31 (5) ◽  
pp. 1324-1332 ◽  
Author(s):  
Giuseppe Matarese ◽  
Veronica Sanna ◽  
Antonio Di Giacomo ◽  
Graham M. Lord ◽  
Jane K. Howard ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Female Mice ◽  
Experimental Autoimmune

scholarly journals Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation

2021 ◽  
Author(s):  
Kseniya S. Aulova ◽  
Andrey E. Urusov ◽  
Ludmila B. Toporkova ◽  
Sergey E. Sedykh ◽  
Yuliya A. Shevchenko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Catalytic Antibodies ◽  
Autoimmune Encephalomyelitis ◽  
Autoimmune Reaction ◽  
Hematopoietic Stem ◽  
Male And Female ◽  
Female Mice ◽  
Experimental Autoimmune

AbstractExact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.

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