Multiple sclerosis

…toneuroinflammatory diseases such as Multiple Sclerosis (MS) orAlzheimer’s disease (AD). Her laboratory combines expertise invascular biology, neuroimmunology and live cell imaging and hasdeveloped sophisticated in vitro and in vivo approaches to studyimmune cell interactions with the brain barriers in health andneuroinflammation.

Experimental autoimmune encephalomyelitis (EAE) is a laboratory model for multiple sclerosis (MS), an autoimmune disease characterized by chronic inflammation in the CNS, associated with demyelination and neurological disorders. Dysbiosis of the gut microbiota is a risk factor for MS. Probiotic strains can modulate the microbiota composition and are considered a therapeutic approach for MS.This study aimed to explore the therapeutic potential of Enterococcus faecium L-3 (E.faecium), a probiotic strain, in modulating gut microbiota, intestinal morphology, and immune responses within an EAE rat

Multiple sclerosis (MS) is by far one of the most commonly occurring demyelinating neuroinflammatory diseases of young adults that is characterized by degradation of the myelin sheath of axons resulting eventually in permanent neurological deficits. Several mediators of the kallikrein-kinin system (KKS) have been identified to be critical contributors to MS pathogenesis and potent direct modulators of neurological functions. In this context, high levels of plasma prekallikrein (PK) were found in active central nervous system (CNS) lesions of MS patients. Recently, Kv7 channels that generate th

Multiple sclerosis (MS) is a prevalent demyelinating disease that primarily affects young adults. Within the realm of MS patients, the extent of disease severity and progression differs greatly across individuals. Studies conducted on post-mortem tissue samples have characterized complex lesion types that diverge significantly on the composition of oligodendrocyte (OLG) lineage cells and their degrees of remyelination, both across different individuals and within each MS patient1. To date, the intrinsic genetic factors that potentially impact OLG-mediated de- and re-myelination in MS lesions,

…(EAE), a recognized animal model for Multiple Sclerosis. In fact both inhibition of S100B activity using pentamidine and of S100B astrocytic synthesis using arundic acid ameliorated clinical and pathologic parameters of the disease (2-4). This study further goes

…inflammatory demyelination in multiple sclerosis (MS) through the activation of CB1 receptors (CB1Rs). Myelinating oligodendrocytes and precursor cells (OPCs) express CB1Rs that mediate protection from excitotoxicity and promote lineage progression but the metabolic implications of

…B cells and is approved to treat multiple sclerosis (MS). Although it is known that ocrelizumab does not completely deplete B cells and B cell reconstitution can be detected in some MS patients, little is known about phenotypes of these remaining as well as repopulating B cells and whether they associate to disease outcomes and/or to changes in other immune cell types. Method: In this study, we performed comprehensive in-depth immune profiling of ocrelizumab-treated MS patients after short-term (a cohort of 31 patients) or long-

…chronic neurological disorders such as multiple sclerosis (MS). Following an acute demyelinating event, damaged myelin is cleared by phagocytes and new myelin sheaths are generated from existing or newly differentiated oligodendrocytes. Our previous studies shed light on the critical impact of functional lipid recycling pathways within phagocytes to enable remyelination of acute lesion. However, to date it is unclear how chronic progressive disease is linked to lipid metabolic pathways. According to the ‘inside-out’ concept of

In multiple sclerosis (MS), oligodendrocyte (OL) degeneration and subsequent demyelination in the central nervous system (CNS) causes neurological impairment. Monocarboxylate transporter 8 (MCT8) may promote OL maturation and myelination by actively transporting thyroid hormone (TH) into the CNS and thereby facilitating key transcription and metabolomic pathways for myelin biogenesis. Diiodothyropropionic acid (DITPA), a synthetic TH-analog, can be transported into the CNS, independent of MCT8 and may promote OL maturation and myelination. In this study, we investigated the potential of DITPA

Calcium is a key intracellular messenger that regulates many vital cellular processes. Calcium signals in oligodendrocytes, the myelinating glia of the CNS, are known to translate environmental information to cellular processes such as proliferation, differentiation and myelination. Myelination is an adaptive process that depends on neuronal activity. We recently demonstrated that neuronal activity in vivo enhances remyelination in demyelinated lesions (Ortiz et al., 2019, JCI Insight). Here, we investigate whether calcium singal in oligodendroglia play a role in remyelination and whether beha

Multiple sclerosis (MS) is a chronic demyelinating disease estimated to affect 2.8 million people globally. Recent human studies indicate that MS is not merely a consequence of demyelination, but it also involves an intricate neuronal component, which remains poorly understood. Here, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to study the neuronal response during autoimmune neuroinflammation, with a particular focus on the prodromal phase, which precedes axonal demyelination. We implemented Targeted Recombination in Active Populations (TRAP) and a compreh

…a 54-year-old female diagnosed with Multiple Sclerosis (MS), presenting with declining cognition and communicative abilities. A comprehensive test battery, incorporating the Addenbrooke’s Cognitive Examination-III Marathi (ACE III- M) and the Frenchay Dysarthria Assessment-Second Edition (FDA-2) revealed Mild Cognitive Impairment and Severe Mixed Dysarthria, respectively—a motor speech disorder contributing to diminished speech in

…as gait dysfunction in patients with Multiple Sclerosis (MS). Here, we assessed the immediate effects of lumbar transcutaneous spinal cord stimulation (tSCS) in a sham-controlled pilot-study of 26 patients with primary or secondary progressive MS.The study protocol included motor assessments before and after application of tSCS. Stimulation electrodes were positioned on the lumbar spine to activate sensory afferents from the legs. All patients conducted a therapy and a sham condition on two separate study days. Stimulation protoc

…neurodegenerative diseases, such as multiple sclerosis (MS) and Alzheimer´s disease (AD). The CSF is the compartment in closest proximity to the central nervous system (CNS) with unique immune cell composition and routine CSF collection is integral for diagnosing various CNS disorders, offering a more practical alternative to assess the CNS. In this study, we described an end-to-end workflow to perform in-depth single-

Background: Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by inflammation-driven synaptic abnormalities. Interleukin 9 (IL-9) is emerging as a pleiotropic cytokine involved in MS pathophysiology.Aim: In this study, we demonstrated that both peripheral and central administration of IL-9 significantly improved clinical disability, reduced neuroinflammation, and mitigated synaptic damage in experimental autoimmune encephalomyelitis (EAE).Results: Biochemical, immunohistochemical, and electrophysiological experiments unmasked previou

Multiple sclerosis (MS) is a chronic neurodegenerative disease that is the leading cause of disability in young adults. The most severe clinical form of MS is the primary progressive (PP). We and others have shown that melatonin (MLT), improves the disease modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) monofasic mouse model of MS. Thus, the objective of this study was to evaluate the therapeutic use of MLT in the neuroinflammation, neurodegeneration and gut dysbiosis in the preclinical model of MS-PP, the progressive EAE (p-EAE).p-EAE was induced in 10-we

Multiple Sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Despite advancements in diagnostic methods, early detection remains challenging. Metabolomic analysis offers a promising, non-invasive approach to identify potential biomarkers for improved diagnostic precision.Cerebrospinal fluid (CSF) and serum samples from 24 healthy controls, 48 MS patients, and 20 Non-MS patients with a range of diverse conditions, including infections, autoimmune disorders, inflammatory issues, and other neurological disorders were collected during lumbar puncture. NMR analysis on a

Multiple Sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) marked by myelin degradation. Myelin is a lipid-rich insulating sheath essential for efficient signal transmission and neuronal health. Despite the critical role of demyelination in MS, existing treatments do not halt disease progression or promote myelin regeneration. Recent insights from our lab underscore microRNA-145 (miR-145) as a pivotal factor hindering oligodendrocyte production, with elevated levels detected in chronic lesions of secondary progressive MS post-mortem brain tissue. To unveil t

…for treating relapsing-remitting multiple sclerosis in diverse age groups. With the ability to cross the blood-brain barrier, FTY720 gradually accumulates within lipid-rich areas of the central nervous system (CNS) by integrating into phospholipid membranes. Consequently, FTY720 can enhance cell membrane fluidity, influencing glial cells and neuronal populations involved in behaviour regulation. This study investigated the impact of chronic FTY720 administration (3.3 μg/ml in ad libitum drinking water f

…Here, we used the cuprizone model of multiple sclerosis to explore the phenotypic signature of astrocytes in the cortex of mice during early demyelination at week 3 (CPZ3), a timepoint of initial demyelination and glia cell activation. Confocal imaging combined with detailed cell-morphometric analysis of cortical astrocytes after 3-dimensional cell reconstruction revealed the morphological phenotype of astrocytes in early demyelination, characterized by thick and long processes

Work over the last decade demonstrates that the myelin sheaths enwrapping axons, classically seen as static insulators, are highly dynamic and respond to axonal activity and experience. This phenomenon, called “myelin plasticity”, goes beyond postnatal stages into adulthood and plays a key role in remodeling neuronal circuits to support adaptive behavior or functional recovery upon injury. Yet the mechanisms are unknown. Here we show that NMDA receptors containing GluN3A subunits are expressed by oligodendrocyte progenitor cells (OPCs) and essentially required for activity-dependent myelin pla

…contribute to autoimmunity such as in multiple sclerosis (MS), a demyelinating CNS disorder. Strikingly, the glial potassium channel KCNJ10 (Kir4.1) can exhibit low to high glycosylated forms and initial works from different laboratories identified variable proportions of MS patients harboring high levels of anti-Kir4.1 IgGs. Using a well-controlled ELISA, six percent of MS patients exhibit high seric l

…to the bigger puzzle of personalized multiple sclerosis (MS) therapies. This study aimed to examine the potential benefit of using four non-coding RNAs (ncRNAs) (miR-141, miR-9, MEG3, and IFNG-AS1) as prognostic and/or diagnostic biomarkers for MS. We also aimed to examine the relationship between two single nucleotide polymorphisms (SNPs), rs547311 and rs205764 on the long intergenic non-coding RNA (linc)-00513 gene (genotyping), and the expression levels of the aforementioned genes (qPCR), in addition to IFN-g (ELISA). The diagnos

…neuroinflammation, especially during multiple sclerosis (MS), and the cytokine engenders permeabilization of in vitro blood-brain barrier (BBB) models. We sought to determine the effect of TWEAK on human brain microvascular endothelial cells (BMECs), specifically the hCMEC/D3 cell line. We used microarray analysis to investigate the transcriptomic changes of hCMEC/D3 induced by rhTWEAK incubation at three timepoints (3h, 12h, and 24h). We identified a set of differentially expressed genes (DEGs) probing the d