Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcranial Magnetic Stimulation Improves Muscle Involvement in Experimental Autoimmune Encephalomyelitis.

ABSTRACT: Skeletal muscle is affected in experimental autoimmune encephalomyelitis (EAE), which is a model of multiple sclerosis that produces changes including muscle atrophy; histological features of neurogenic involvement, and increased oxidative stress. In this study, we aimed to evaluate the therapeutic effects of transcranial magnetic stimulation (TMS) on the involvement of rat skeletal muscle and to compare them with those produced by natalizumab (NTZ). EAE was induced by injecting myelin oligodendrocyte glycoprotein (MOG) into Dark Agouti rats. Both treatments, NTZ and TMS, were implemented from day 15 to day 35. Clinical severity was studied, and after sacrifice, the soleus and extensor digitorum longus muscles were extracted for subsequent histological and biochemical analysis. The treatment with TMS and NTZ had a beneficial effect on muscle involvement in the EAE model. There was a clinical improvement in functional motor deficits, atrophy was attenuated, neurogenic muscle lesions were reduced, and the level of oxidative stress biomarkers was lower in both treatment groups. Compared to NTZ, the best response was obtained with TMS for all the parameters analyzed. The myoprotective effect of TMS was higher than that of NTZ. Thus, the use of TMS may be an effective strategy to reduce muscle involvement in multiple sclerosis.

SUBMITTER: Pena-Toledo MA

PROVIDER: S-EPMC8395284 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis.

Project description:Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model-experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.

| S-EPMC8227256 | biostudies-literature

Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis.

Project description:Calcitonin Gene-Related Peptide (CGRP) inhibits microglia inflammatory activation in vitro. We here analyzed the involvement of CGRP and Receptor Component Protein (RCP) in experimental autoimmune encephalomyelitis (EAE). Alpha-CGRP deficiency increased EAE scores which followed the scale alpha-CGRP null>heterozygote>wild type. In wild type mice, CGRP delivery into the cerebrospinal fluid (CSF) 1) reduced chronic EAE (C-EAE) signs, 2) inhibited microglia activation (revealed by quantitative shape analysis), and 3) did not alter GFAP expression, cell density, lymphocyte infiltration, and peripheral lymphocyte production of IFN-gamma, TNF-alpha, IL-17, IL-2, and IL-4. RCP (probe for receptor involvement) was expressed in white matter microglia, astrocytes, oligodendrocytes, and vascular-endothelial cells: in EAE, also in infiltrating lymphocytes. In relapsing-remitting EAE (R-EAE) RCP increased during relapse, without correlation with lymphocyte density. RCP nuclear localization (stimulated by CGRP in vitro) was I) increased in microglia and decreased in astrocytes (R-EAE), and II) increased in microglia by CGRP CSF delivery (C-EAE). Calcitonin like receptor was rarely localized in nuclei of control and relapse mice. CGRP increased in motoneurons. In conclusion, CGRP can inhibit microglia activation in vivo in EAE. CGRP and its receptor may represent novel protective factors in EAE, apparently acting through the differential cell-specific intracellular translocation of RCP.

| S-EPMC4485954 | biostudies-literature

Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2.

Project description:Multiple sclerosis (MS) is a complex multifactorial disease that results from the interplay between environmental factors and a susceptible genetic background. Experimental autoimmune encephalomyelitis (EAE) has been widely used to investigate the mechanisms underlying MS pathogenesis. Chemokines, such as CCL2, are involved in the development of EAE. We have previously shown that thiamine deficiency (TD) induced CCL2 in neurons. We hypothesized that TD may affect the pathogenesis of EAE. In this study, EAE was induced in C57BL/6J mice by the injection of myelin oligodendroglial glycoprotein (MOG) peptides 35-55 with or without TD. TD aggravated the development of EAE, which was indicated by clinical scores and pathologic alterations in the spinal cord. TD also accelerated the development of EAE in an adoptive transfer EAE model. TD caused microglial activation and a drastic increase (up 140%) in leukocyte infiltration in the spinal cord of the EAE mice; specifically, TD increased Th1 and Th17 cells. TD upregulated the expression of CCL2 and its receptor CCR2 in the spinal cord of EAE mice. Cells in peripheral lymph node and spleen isolated from MOG-primed TD mice showed much stronger proliferative responses to MOG. CCL2 stimulated the proliferation and migration of T lymphocytes in vitro. Our results suggested that TD exacerbated the development of EAE through activating CCL2 and inducing pathologic inflammation.

| S-EPMC4135011 | biostudies-literature

Neurophysics Assessment of the Muscle Bioenergy Generated by Transcranial Magnetic Stimulation.

Project description:The content of the rectified motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) has ambiguously been assessed without the precision that energy calculation deserves. This fact has misled data interpretation and misguided biomedical interventions. To definitively fill the gap that exits in the neurophysics processing of these signals, we computed, in Walls ( W^ ), the bioenergy within the rectified MEP recorded from the human first digitorum index (FDI) muscle at rest and under isometric contraction. We also gauged the biowork exerted by this muscle. Here we show that bioenergy and biowork can accurately and successfully be assessed, validated, and determined in W^ from MEP signals induced by TMS, regardless of knowing the mathematical expression of the function of the signal. Our novel neurophysics approach represents a dramatic paradigm shift in analysis and interpretation of the content of the MEP and will give a true meaning to the content of rectified signals. Importantly, this innovative approach allowed unveiling that women exerted more bioenergy than men at the magnetic stimulations used in this study. Revisitation of conclusions drawn from studies published elsewhere assessing rectified EMG signals that have used ambiguous units is strongly recommended.

| S-EPMC6750091 | biostudies-literature

Microbiome Methods in Experimental Autoimmune Encephalomyelitis.

Project description:Microbiome composition studies are increasingly shedding light on animal models of disease. This paper describes a protocol for analyzing the gut microbiome composition prior to and after the induction of mice to experimental autoimmune encephalomyelitis (EAE), the principal animal model of the human neuroinflammatory demyelinating disease multiple sclerosis (MS). We also address and provide data assessing the impact of mice reared in different animal facilities on EAE induction. Furthermore, we discuss potential regulators of the gut-microbiome-brain axis (GMBA) in relation to neuroinflammation and implications on demyelinating disease states. Our results suggest that mice reared in different animal facilities produce different levels of EAE induction. These results highlight the importance of accounting for consistent environmental conditions when inducing EAE and other animal models of disease. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Study of the composition of the gut microbiome in the neuroinflammatory model of experimental autoimmune encephalomyelitis Basic Protocol 2: Experimental procedures for DNA extraction and microbiome analysis.

| S-EPMC9540342 | biostudies-literature

MAIT cells in experimental autoimmune encephalomyelitis (EAE)

Project description:Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS) most likely caused by autoreactive T cells. Mucosal-associated invariant T (MAIT) cells are characterized by a semi-invariant T cell receptor (TCR) with which they recognize 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a metabolite of the riboflavin (vitamin B2) pathway only present in yeast and bacteria. MAIT cells have been detected in inflamed brain lesions of MS patients. However, functional analyses of CNS-infiltrating MAIT cells are lacking and require a characterisation in the MS animal model experimental autoimmune encephalomyelitis (EAE).

2024-09-30 | GSE234291 | GEO

Repetitive transcranial magnetic stimulation improves Parkinson's freezing of gait via normalizing brain connectivity.

Project description:Robust, effective treatments for Parkinson's freezing of gait remain elusive. Our previous study revealed beneficial effects of high-frequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson's disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset of 30 patients with freezing of gait (verum group: N = 20; sham group: N = 10) who participated the aforementioned rTMS study underwent another scan after the treatments. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. Results showed that the freezing of gait biomarker was negatively correlated with Freezing of Gait Questionnaire score (r = -0.6723, p < 0.0001); while the Parkinson's disease biomarker was negatively correlated with MDS-UPDRS motor score (r = -0.7281, p < 0.0001). After the rTMS treatment, both the freezing of gait biomarker (0.326 ± 0.125 vs. 0.486 ± 0.193, p = 0.0071) and Parkinson's disease biomarker (0.313 ± 0.126 vs. 0.379 ± 0.155, p = 0.0378) were significantly improved in the verum group; whereas no significant biomarker changes were found in the sham group. Our findings indicate that high-frequency rTMS over the supplementary motor area confers the beneficial effect jointly through normalizing abnormal brain functional connectivity patterns specifically associated with freezing of gait, in addition to normalizing overall disrupted connectivity patterns seen in Parkinson's disease.

| S-EPMC7368045 | biostudies-literature

Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis.

Project description:Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease but the molecular mechanisms underlying neurodegenerative aspects of the disease are poorly understood. microRNAs (miRNAs) are powerful regulators of gene expression that regulate numerous mRNAs simultaneously and can thus regulate programs of gene expression. Here, we describe miRNA expression in neurons captured from mice subjected to experimental autoimmune encephalomyelitis (EAE), a model of central nervous system (CNS) inflammation. Lumbar motor neurons and retinal neurons were laser captured from EAE mice and miRNA expression was assessed by next-generation sequencing and validated by qPCR. We describe 14 miRNAs that are differentially regulated in both neuronal subtypes and determine putative mRNA targets though in silico analysis. Several upregulated neuronal miRNAs are predicted to target pathways that could mediate repair and regeneration during EAE. This work identifies miRNAs that are affected by inflammation and suggests novel candidates that may be targeted to improve neuroprotection in the context of pathological inflammation.

| S-EPMC6128870 | biostudies-other

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection.

Project description:Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site. Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds. Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators. Here, we provide evidence that an exception to this pattern is found in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that cell damage induced by EAE does not lead to increase in eCBs, even though cannabinoid receptors are functional because synthetic cannabinoid agonists are known to confine EAE-induced lesions. This lack of eCB increase is likely due to IFN-gamma, which is released by primed T cells invading the CNS. We show that IFN-gamma disrupts the functionality of purinergic P2X7 receptors, a key step controlling eCB production by microglia, the main source of eCBs in brain. Accordingly, induction of EAE in P2X7-/- mice results in even lower eCB levels and more pronounced cell damage than in wild-type mice. Our data suggest that the high level of CNS IFN-gamma associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis.

| S-EPMC1458883 | biostudies-other

Blocking GluR2-GAPDH ameliorates experimental autoimmune encephalomyelitis.

Project description:OBJECTIVE: Multiple sclerosis (MS) is the most common disabling neurological disease of young adults. The pathophysiological mechanism of MS remains largely unknown and no cure is available. Current clinical treatments for MS modulate the immune system, with the rationale that autoimmunity is at the core of MS pathophysiology. METHODS: Experimental autoimmune encephalitis (EAE) was induced in mice with MOG35-55 and clinical scoring was performed to monitor signs of paralysis. EAE mice were injected intraperitoneally with TAT-fusion peptides daily from day 10 until day 30 after immunization, and their effects were measured at day 17 or day 30. RESULTS: We report a novel target for the development of MS therapy, which aimed at blocking glutamate-mediated neurotoxicity through targeting the interaction between the AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid) receptor and an interacting protein. We found that protein complex composed of the GluR2 subunit of AMPA receptors and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was present at significantly higher levels in postmortem tissue from MS patients and in EAE mice, an animal model for MS. Next, we developed a peptide that specifically disrupts the GluR2 -GAPDH complex. This peptide greatly improves neurological function in EAE mice, reduces neuron death, rescues demyelination, increases oligodendrocyte survival, and reduces axonal damage in the spinal cords of EAE mice. More importantly, our peptide has no direct suppressive effect on naive T-cell responses or basal neurotransmission. INTERPRETATION: The GluR2 -GAPDH complex represents a novel therapeutic target for the development of medications for MS that work through a different mechanism than existing treatments.

| S-EPMC4402084 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data