This study aimed to explore the intricate relationship between mitochondrial dysfunction, infection, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged and C57BL/6J wild-type mice immunized with EBNA1 or with active experimental autoimmune encephalomyelitis (EAE) induction by the myelin oligodendrocyte glycoprotein (MOG) peptide. The mice developed more severe EAE than the wild-type mice.
View Article and Find Full Text PDFMany RNA-binding proteins (RBPs) are linked to the dysregulation of RNA metabolism in motor neuron diseases (MNDs). However, the molecular mechanisms underlying MN vulnerability have yet to be elucidated. Here, we found that such an RBP, Quaking5 (Qki5), contributes to formation of the MN-specific transcriptome profile, termed "MN-ness," through the posttranscriptional network and maintenance of the mature MNs.
View Article and Find Full Text PDFOligodendrocytes (OLs) are the myelin-forming cells in the CNS that support neurons through the insulating sheath of axons. This unique feature and developmental processes are achieved by extrinsic and intrinsic gene expression programs, where RNA-binding proteins can contribute to dynamic and fine-tuned post-transcriptional regulation. Here, we identified SECIS-binding protein 2-like (Sbp2l), which is specifically expressed in OLs by integrated transcriptomics.
View Article and Find Full Text PDFIntroduction: Myelin-oligodendrocyte glycoprotein antibody (MOG)-associated disorder (MOGAD) is a recently identified immune-mediated inflammatory disorder of the central nervous system (CNS). The significance of oligoclonal bands (OCBs) is not fully elucidated. This study investigated the clinical differences between patients with MOGAD who tested positive or negative for OCBs.
View Article and Find Full Text PDFNeuroinflammation can be triggered by microbial products disrupting immune regulation. In this study, we investigated the levels of IgG1, IgG2, IgG3, and IgG4 subclasses against the heat shock protein (HSP)70 peptide and lipopentapeptide (MAP_Lp5) derived from subsp. (MAP) in the blood samples of Japanese and Italian individuals with relapsing remitting multiple sclerosis (MS).
View Article and Find Full Text PDFExperimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) requires immunization by a MOG peptide emulsified in complete Freund's adjuvant (CFA) containing inactivated Mycobacterium tuberculosis. The antigenic components of the mycobacterium activate dendritic cells to stimulate T-cells to produce cytokines that promote the Th1 response via toll-like receptors. Therefore, the amount and species of mycobacteria present during the antigenic challenge are directly related to the development of EAE.
View Article and Find Full Text PDFMultiple sclerosis is the most common immune-mediated disorder affecting the central nervous system in young adults but still has no cure. Bacillus Calmette-Guérin (BCG) vaccine is reported to have non-specific anti-inflammatory effects and therapeutic benefits in autoimmune disorders including multiple sclerosis. However, the precise mechanism of action of BCG and the host immune response to it remain unclear.
View Article and Find Full Text PDFMyasthenia gravis (MG) development is female-dominant in younger patients and male-dominant in older patients. The reason for the sex-ratio inversion in elderly MG patients remains unclear. One possible explanation is the decrease in androgen secretion that occurs with aging, as androgen has an immunosuppressive function.
View Article and Find Full Text PDFObjective: Recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems' immune responses.
Methods: EAE was induced in female mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity.
View Article and Find Full Text PDFHerein, we combined neurite orientation dispersion and density imaging (NODDI) and synthetic magnetic resonance imaging (SyMRI) to evaluate the spatial distribution and extent of gray matter (GM) microstructural alterations in patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD). The NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) and SyMRI (myelin volume fraction [MVF]) measures were compared between age- and sex-matched groups of 30 patients with RRMS (6 males and 24 females; mean age, 51.43 ± 8.
View Article and Find Full Text PDFIntroduction: Despite differences in the pathogenesis and treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), it remains difficult to distinguish them. In this study, we aimed to discriminate between MS and NMOSD using diffusion tensor imaging (DTI), free water (FW) imaging, and neurite orientation dispersion and density imaging (NODDI).
Methods: Thirty patients with relapsing-remitting (RR) MS, 18 NMOSD patients with positive anti-aquaporin-4 immunoglobulin G seroreactivity, and 20 age- and sex- matched currently healthy subjects underwent MRI.
Background: Anti-aquaporin 4 (AQP4) antibody (AQP4-Ab) is involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism involved in AQP4-Ab production remains unclear.
Methods: We analyzed the immunophenotypes of patients with NMOSD and other neuroinflammatory diseases as well as healthy controls (HC) using flow cytometry.
The Bacillus Calmette-Guerin (BCG) vaccine can modulate the immune response via antigen-specific immune response, but also it can confer nonspecific protection and therapeutic benefits in several neurological conditions through different heterologous effects of vaccination. However, the precise mechanism of action of BCG remains unclear. In this review, different mechanisms underlying BCG-mediated immunity will be explained in animal models that reflects characteristic feature of neuroinflammatory and neurodegenerative disorders such as multiple sclerosis, Alzheimer's and Parkinson's diseases.
View Article and Find Full Text PDFWe herein report a case of multiple myeloma and polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome. The patient experienced exacerbated gait disturbance due to weakness and numbness in the lower limbs. Thoracic magnetic resonance imaging revealed an extramedullary tumor with spinal compression that required surgical resection.
View Article and Find Full Text PDFTo investigate whether antibody production against mycobacterium avium subsp. paratuberculosis (MAP) is related to clinical characteristics of multiple sclerosis (MS) and human leukocyte antigen (HLA) alleles, IgG antibody against three MAP peptides and two human peptides homologous to MAP were measured in sera from 103 MS patients and 50 healthy controls (HCs). MS patients had higher IgG levels against MAP2694 (MAP2694-IgG) than HCs, while the other antibodies were comparable.
View Article and Find Full Text PDFNeuroinflammation plays an important role in the pathogenesis of several neurodegenerative disorders. To elucidate the effects of the mitophagy-related gene Parkin on neuroinflammation, we used a mouse model of experimental autoimmune encephalomyelitis (EAE). Female Parkin and female wild type control mice were immunized with myelin oligodendrocyte glycoprotein to develop active EAE.
View Article and Find Full Text PDFBackground: Mitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS).
Objective: To determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders.
Methods: Protein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched controls.
Purpose: We hypothesize that myelin is more susceptible to damage over time than axons. We investigated the association between the estimated duration from the onset of multiple sclerosis (MS) plaques and myelin- and axon-related quantitative synthetic magnetic resonance imaging (SyMRI) and neurite orientation dispersion and density imaging (NODDI) metrics.
Methods: We analyzed 31 patients with MS with 73 newly appeared plaques.
Multiple sclerosis and neuromyelitis optica spectrum disorders are both neuroinflammatory diseases and have overlapping clinical manifestations. We developed a convolutional neural network model that differentiates between the two based on magnetic resonance imaging data. Thirty-five patients with relapsing-remitting multiple sclerosis and eighteen age-, sex-, disease duration-, and Expanded Disease Status Scale-matched patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders were included in this study.
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