scholarly journals miRNA-Dependent CD4+ T Cell Differentiation in the Pathogenesis of Multiple Sclerosis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Justyna Basak ◽  
Ireneusz Majsterek
Keyword(s):  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Regulation Of Gene Expression ◽  
Chronic Inflammatory Condition ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Signal Cascades ◽  
The Impact

Multiple sclerosis (MS) is characterized by multifocal lesions, chronic inflammatory condition, and degenerative processes within the central nervous system (CNS) leading to demyelination. The most important cells involved in its pathogenesis are those which are CD4+, particularly proinflammatory Th1/Th17 and regulatory Treg. Signal cascades associated with CD4+ differentiation are regulated by microRNAs (miRNAs): short, single-stranded RNAs, responsible for negative regulation of gene expression at the posttranscriptional level. Several miRNAs have been consistently reported as showing dysregulated expression in MS, and their expression patterns may be elevated or decreased, depending on the function of specific miRNA in the immune system. Studies in MS patients indicate that, among others, miR-141, miR-200a, miR-155, miR-223, and miR-326 are upregulated, while miR-15b, miR-20b, miR-26a, and miR-30a are downregulated. Dysregulation of these miRNAs may contribute to the imbalance between pro- and anti-inflammatory processes, since their targets are associated with the regulation of Th1/Th17 and Treg cell differentiation. Highly expressed miRNAs can in turn suppress translation of key Th1/Th17 differentiation inhibitors. miRNA dysregulation may result from the impact of various factors at each stage of their biogenesis. Immature miRNA undergoes multistage transcriptional and posttranscriptional modifications; therefore, any protein involved in the processing of miRNAs can potentially lead to disturbances in their expression. Epigenetic modifications that have a direct impact on miRNA gene transcription may also play an important role.

HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

2010 ◽  
Vol 16 (10) ◽  
pp. 1173-1177 ◽  
Author(s):  
M. Shahbazi ◽  
H. Ebadi ◽  
D. Fathi ◽  
D. Roshandel ◽  
M. Mohamadhosseni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Promoter Polymorphism ◽  
Exact Test ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Pcr Method ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

scholarly journals Validation and cross-cultural adaptation of sexual dysfunction modified scale in multiple sclerosis for Brazilian population

2015 ◽  
Vol 73 (8) ◽  
pp. 681-687 ◽  
Author(s):  
Raquel Ataíde Peres da Silva ◽  
Guilherme Sciascia do Olival ◽  
Lívia Palma Stievano ◽  
Vania Balardin Toller ◽  
Sergio Semeraro Jordy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sexual Dysfunction ◽  
Cultural Adaptation ◽  
Chronic Inflammatory Disease ◽  
Cross Cultural ◽  
Brazilian Population ◽  
Control Group ◽  
Cross Cultural Adaptation ◽  
The Central Nervous System ◽  
The Impact

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). These patients suffer from various comorbidities, including sexual dysfunction (SD). The lesions of MS may affect regions of the CNS along the pathway of sexual response. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that assesses sexual dysfunction. Adapt and validate the MSISQ-19 to Brazilian patients with MS. 204 individuals were evaluated, 134 patients with MS and 70 healthy persons for the control group. It was determined reproducibility, validity, internal consistency and sensitivity of the MSISQ-19-BR. Among patients with MS, 54.3% of male and 71.7% of female presented some kind of SD. In the control group the results were 12.5% and 19.5%, respectively. The MSISQ-19-BR is reproducible, reliable and valid for the Brazilian population and may be used as a tool for assessing the impact of sexual dysfunction in patients with MS.

The impact of hypoxia on blood-brain, blood-CSF and CSF-brain barriers

2021 ◽  
Author(s):  
Jeff F. Dunn ◽  
Albert M Isaacs
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Cellular Structures ◽  
Bacterial Toxin ◽  
Blood Brain ◽  
High Altitude Cerebral Edema ◽  
The Central Nervous System ◽  
Neurological Conditions ◽  
The Impact ◽  
Brain Barriers

The blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB) and CSF-brain barriers (CSFBB) are highly regulated barriers in the central nervous system comprising of complex multi-cellular structures that separate nerves and glia from blood and cerebrospinal fluid, respectively. Barrier damage has been implicated in the pathophysiology of diverse hypoxia-related neurological conditions including stroke, multiple sclerosis, hydrocephalus and high-altitude cerebral edema. Much is known about damage to the BBB in response to hypoxia but much less is known about the BCSFB and CSFBB. Yet it is known that these other barriers are implicated in damage after hypoxia or inflammation. In the 1950s, it was shown that the rate of radionucleated human serum albumin passage from plasma to CSF was 5-times higher during hypoxic than normoxic conditions in dogs, due to blood-CSF barrier disruption. Severe hypoxia due to administration of the bacterial toxin, lipopolysaccharide (LPS) is associated with disruption of the CSFBB. This review discusses the anatomy of the BBB, BCSFB and CSFBB, and the impact of hypoxia and associated inflammation on the regulation of those barriers.

scholarly journals Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Ireland ◽  
Nancy Monson
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
The Central Nervous System ◽  
Potential Impact ◽  
Anti Cd20 ◽  
The Impact ◽  
Ms Pathogenesis

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

scholarly journals A Review of Various Antioxidant Compounds and their Potential Utility as Complementary Therapy in Multiple Sclerosis

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1528 ◽  
Author(s):  
Elzbieta Dorota Miller ◽  
Angela Dziedzic ◽  
Joanna Saluk-Bijak ◽  
Michal Bijak
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Complex Disease ◽  
Early Stage ◽  
Symptomatic Treatment ◽  
Complementary Therapy ◽  
Antioxidant Compounds ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Stress Mediators

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS). The etiology of this multifactorial disease has not been clearly defined. Conventional medical treatment of MS has progressed, but is still based on symptomatic treatment. One of the key factors in the pathogenesis of MS is oxidative stress, enhancing inflammation and neurodegeneration. In MS, both reactive oxygen and nitrogen species are formed in the CNS mainly by activated macrophages and microglia structures, which can lead to demyelination and axon disruption. The course of MS is associated with the secretion of many inflammatory and oxidative stress mediators, including cytokines (IL-1b, IL-6, IL-17, TNF-α, INF-γ) and chemokines (MIP-1a, MCP-1, IP10). The early stage of MS (RRMS) lasts about 10 years, and is dominated by inflammatory processes, whereas the chronic stage is associated with neurodegenerative axon and neuron loss. Since oxidative damage has been known to be involved in inflammatory and autoimmune-mediated processes, antioxidant therapy could contribute to the reduction or even prevention of the progression of MS. Further research is needed in order to establish new aims for novel treatment and provide possible benefits to MS patients. The present review examines the roles of oxidative stress and non-pharmacological anti-oxidative therapies in MS.

scholarly journals Multiple sclerosis: Implications for future research on postural control and gait

2020 ◽  
Vol 14 (2) ◽  
pp. 46-49
Author(s):  
Felipe Balistieri Santinelli ◽  
Emerson Sebastião ◽  
Marcela de Oliveira ◽  
Fabio Augusto Barbieri
Keyword(s):  
Multiple Sclerosis ◽  
Postural Control ◽  
Future Research ◽  
Insufficient Information ◽  
Future Studies ◽  
Rehabilitation Programs ◽  
The Central Nervous System ◽  
The Impact ◽  
Gait Impairments

The objective of this letter is to provide a perspective on the impact of multiple sclerosis (MS) on postural control and gait and suggestions for future studies. Although studies on MS with postural control and gait have been carried out for some time, in Brazil and in the World, there is still insufficient information on MS and impairments in postural control and gait.Postural control and gait impairments are recognized to cause several problems for people with MS, these being two of the symptoms that most affect quality of life.Here, we present studies that have investigated impairments in postural control and gait using different experimental designs and discuss the adaptations of the central nervous system (CNS) due to the damage caused by MS.We recommend future studies focus on how the CNS is organized towards postural control and gait, with a better ecological approach, which could assist the development of rehabilitation programs.

scholarly journals Drp1 is widely, yet heterogeneously, distributed in the mouse central nervous system

2020 ◽  
Author(s):  
Ting-Ting Luo ◽  
Chun-Qiu Dai ◽  
Jia-Qi Wang ◽  
Zheng-Mei Wang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Malignant Glioma ◽  
Expression Patterns ◽  
Heterogeneous Distribution ◽  
Human Malignant Glioma ◽  
The Central Nervous System ◽  
The Impact ◽  
The Relationship ◽  
Mouse Central Nervous System

Abstract Objectives: Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good approach to targeted treatment or prognosis. Methods: We visualized the distribution of Drp1 in different brain regions and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 in GABAergic neurons. We also further analyzed Drp1 expression in human malignant glioma tissue. Results : Drp1 was widely but heterogeneously distributed in the central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscopy, the distribution of Drp1 was higher in dendrites than other areas in neurons, and only a small amount of Drp1 was localized in mitochondria. In human malignant glioma, the fluorescence intensity of Drp1 increased from grade I-III, while grade IV showed a declining trend. Conclusion: In this study, we observed a wide heterogeneous distribution of Drp1 in the central nervous system, which might be related to the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may will to therapeutic guidance in the clinic.

scholarly journals Key protein-coding genes related to microglia in immune regulation and inflammatory response induced by epilepsy

2012 ◽  
Vol 18 (6) ◽  
pp. 9563-9578
Author(s):  
Jing Cao ◽  
◽  
Hui Gan ◽  
Han Xiao ◽  
Hui Chen ◽  
...  
Keyword(s):  
Immune Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Polymerase Chain Reaction Analysis ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
And Migration ◽  
New Biomarkers

<abstract> <p>Several studies have shown a link between immunity, inflammatory processes, and epilepsy. Active neuroinflammation and marked immune cell infiltration occur in epilepsy of diverse etiologies. Microglia, as the first line of defense in the central nervous system, are the main effectors of neuroinflammatory processes. Discovery of new biomarkers associated with microglia activation after epileptogenesis indicates that targeting specific molecules may help control seizures. In this research, we used a combination of several bioinformatics approaches, including RNA sequencing, to explore differentially expressed genes (DEGs) in epileptic lesions and control samples, and to construct a protein-protein interaction (PPI) network for DEGs, which was examined utilizing plug-ins in Cytoscape software. Finally, we aimed to identify 10 hub genes in immune and inflammation-related sub-networks, which were subsequently validated in real-time quantitative polymerase chain reaction analysis in a mouse model of kainic acid-induced epilepsy. The expression patterns of nine genes were consistent with sequencing outcomes. Meanwhile, several genes, including CX3CR1, CX3CL1, GPR183, FPR1, P2RY13, P2RY12 and LPAR5, were associated with microglial activation and migration, providing novel candidate targets for immunotherapy in epilepsy and laying the foundation for further research.</p> </abstract>

scholarly journals Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Talia Bergaglio ◽  
Antonio Luchicchi ◽  
Geert J. Schenk
Keyword(s):  
Multiple Sclerosis ◽  
Tissue Injury ◽  
Neuronal Loss ◽  
Glia Cells ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Triggering Mechanisms ◽  
Engine Failure ◽  
Inside Out ◽  
Ms Pathogenesis

Multiple Sclerosis (MS) is a complex and chronic disease of the central nervous system (CNS), characterized by both degenerative and inflammatory processes leading to axonal damage, demyelination, and neuronal loss. In the last decade, the traditional outside-in standpoint on MS pathogenesis, which identifies a primary autoimmune inflammatory etiology, has been challenged by a complementary inside-out theory. By focusing on the degenerative processes of MS, the axo-myelinic system may reveal new insights into the disease triggering mechanisms. Oxidative stress (OS) has been widely described as one of the means driving tissue injury in neurodegenerative disorders, including MS. Axonal mitochondria constitute the main energy source for electrically active axons and neurons and are largely vulnerable to oxidative injury. Consequently, axonal mitochondrial dysfunction might impair efficient axo-glial communication, which could, in turn, affect axonal integrity and the maintenance of axonal, neuronal, and synaptic signaling. In this review article, we argue that OS-derived mitochondrial impairment may underline the dysfunctional relationship between axons and their supportive glia cells, specifically oligodendrocytes and that this mechanism is implicated in the development of a primary cytodegeneration and a secondary pro-inflammatory response (inside-out), which in turn, together with a variably primed host’s immune system, may lead to the onset of MS and its different subtypes.

scholarly journals What Are the Participants’ Perspectives of Taking Melatonin for the Treatment of Nocturia in Multiple Sclerosis? A Qualitative Study Embedded within a Double-Blind RCT

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Rafiyah Khan ◽  
Alan Uren ◽  
Luke Canham ◽  
David Cottrell ◽  
Marcus J. Drake ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Psychological Functioning ◽  
Qualitative Interviews ◽  
Negative Effects ◽  
Double Blind ◽  
Trial Treatment ◽  
The Central Nervous System ◽  
Qualitative Exploration ◽  
The Impact

Background. Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive, and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods. 17 semistructured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results. Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night, and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep, and energy and negative effects including lethargy, a lack of significant change, and physical side effects including vivid dreams. Conclusion. This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects.

Sign in / Sign up

Export Citation Format

Share Document