Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy.

ABSTRACT: Microglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.

SUBMITTER: Acharjee S

PROVIDER: S-EPMC8275680 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord.

Project description:Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice via modulation of apoptotic pathways, but other signaling pathways were not previously covered. Therefore, the aim of the present study was to further investigate the effects of Sildenafil treatment on autophagy and nitrosative stress signaling pathways in EAE. 24 female C57BL/6 mice were divided into the following groups: (A) Control - received only water; (B) EAE - EAE untreated mice; (C) SILD - EAE mice treated with 25mg/kg of Sildenafil s.c. The results showed that EAE mice presented a pro-nitrosative profile characterized by high tissue nitrite levels, lowered levels of p-eNOS and high levels of iNOS. Furthermore, decreased levels of LC3, beclin-1 and ATG5, suggests impaired autophagy, and decreased levels of AMPK in the spinal cord were also detected in EAE mice. Surprisingly, treatment with Sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK. In conclusion, we propose that Sildenafil alleviates EAE by activating autophagy via the eNOS-NO-AMPK-mTOR-LC3-beclin1-ATG5 and eNOS-NO-AMPK-mTOR-CREB-BDNF pathways in the spinal cord.

| S-EPMC8156813 | biostudies-literature

AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.

Project description:The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK-AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.

| S-EPMC7961553 | biostudies-literature

Differential expression of genes in spinal cord folowing experimental autoimmune encephalomyelitis (EAE) in mice.

Project description:Microarrays were used to identify genes that were differently expressed in mouse spinal cord as a resut of experimental autoimmune encephalomyelitis (EAE), which is a model for demyelinating disease. Mice were injected with PLP peptide or vechicle.

2013-08-01 | E-GEOD-44989 | biostudies-arrayexpress

Differential expression of genes in spinal cord folowing experimental autoimmune encephalomyelitis (EAE) in mice.

2013-08-01 | GSE44989 | GEO

Increased carbonylation, protein aggregation and apoptosis in the spinal cord of mice with experimental autoimmune encephalomyelitis.

Project description:Previous work from our laboratory implicated protein carbonylation in the pathophysiology of both MS (multiple sclerosis) and its animal model EAE (experimental autoimmune encephalomyelitis). Subsequent in vitro studies revealed that the accumulation of protein carbonyls, triggered by glutathione deficiency or proteasome inhibition, leads to protein aggregation and neuronal cell death. These findings prompted us to investigate whether their association can be also established in vivo. In the present study, we characterized protein carbonylation, protein aggregation and apoptosis along the spinal cord during the course of MOG (myelin-oligodendrocyte glycoprotein)(35-55) peptide-induced EAE in C57BL/6 mice. The results show that protein carbonyls accumulate throughout the course of the disease, albeit by different mechanisms: increased oxidative stress in acute EAE and decreased proteasomal activity in chronic EAE. We also show a temporal correlation between protein carbonylation (but not oxidative stress) and apoptosis. Furthermore, carbonyl levels are significantly higher in apoptotic cells than in live cells. A high number of juxta-nuclear and cytoplasmic protein aggregates containing the majority of the oxidized proteins are present during the course of EAE. The LC3 (microtubule-associated protein light chain 3)-II/LC3-I ratio is significantly reduced in both acute and chronic EAE indicating reduced autophagy and explaining why aggresomes accumulate in this disorder. Taken together, the results of the present study suggest a link between protein oxidation and neuronal/glial cell death in vivo, and also demonstrate impaired proteostasis in this widely used murine model of MS.

| S-EPMC3620690 | biostudies-literature

Altered proteolytic events in experimental autoimmune encephalomyelitis discovered by iTRAQ shotgun proteomics analysis of spinal cord.

Project description:BackgroundAbnormal activation of protease activities during experimental autoimmune encephalomyelitis (EAE) in rats, a rodent model of multiple sclerosis, have been implicated in either the direct destruction of myelin components or the intracellular signal transduction pathways that lead to lymphocyte infiltration, oligodendrocyte destruction, neuronal dysfunctions and axonal degeneration. The identification of changes in regulated proteolytic events during EAE is crucial for uncovering activated proteases that may underline the pathological features such as inflammation and demyelination. We searched for either non-tryptic or semi-tryptic peptides from a previous shotgun proteomics study using isobaric tags for relative and absolute quantification (iTRAQ) to compare the proteomes of normal and EAE rat lumbar spinal cords.ResultsWe discovered that several proteins, such as alpha1-macroglobulin, a protease inhibitor, alpha1B-glycoprotein, beta2-microglobulin, neurofilament light polypeptide and sulfated glycoprotein 1 had non-tryptic peptide iTRAQ ratios that were substantially different from the overall protein iTRAQ ratios, suggesting that such peptides may be markers for the proteolytic products generated by the protease(s) altered during EAE. Indeed, subsequent Western blotting confirmed the dysregulation of specific protein cleavages in EAE tissues. Additional proteolytic changes in alpha2-macroglobulin, another protease inhibitor similar to alpha1-macroglobulin was also observed.ConclusionThe results from this study revealed changes among both neuronal protein processing and endogenous proteolysis modulators in EAE animals. This information may provide a rationale for protease inhibitor-based therapeutic interventions for multiple sclerosis.

| S-EPMC2716311 | biostudies-literature

Cytokine-regulated neutrophil recruitment is required for brain but not spinal cord inflammation during experimental autoimmune encephalomyelitis.

Project description:Multiple sclerosis (MS) is an autoimmune disease in which inflammatory lesions lead to tissue injury in the brain and/or spinal cord. The specific sites of tissue injury are strong determinants of clinical outcome in MS, but the pathways that determine whether damage occurs in the brain or spinal cord are not understood. Previous studies in mouse models of MS demonstrated that IFN-? and IL-17 regulate lesion localization within the brain; however, the mechanisms by which these cytokines mediate their effects have not been identified. In the present study, we show that IL-17 promoted, but IFN-? inhibited, ELR(+) chemokine-mediated neutrophil recruitment to the brain, and that neutrophil infiltration was required for parenchymal tissue damage in the brain. In contrast, IFN-? promoted ELR(+) chemokine expression and neutrophil recruitment to the spinal cord. Surprisingly, tissue injury in the spinal cord did not exhibit the same dependence on neutrophil recruitment that was observed for the brain. Our results demonstrate that the brain and spinal cord exhibit distinct sensitivities to cellular mediators of tissue damage, and that IL-17 and IFN-? differentially regulate recruitment of these mediators to each microenvironment. These findings suggest an approach toward tailoring therapies for patients with distinct patterns of neuroinflammation.

| S-EPMC4123857 | biostudies-literature

Identification of differentially expressed proteins in experimental autoimmune encephalomyelitis (EAE) by proteomic analysis of the spinal cord.

Project description:The present study used isobaric tags for relative and absolute quantitation (iTRAQ) to identify novel targets in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The expression of 41 proteins was significantly altered in the inflamed spinal cord. Twenty of these are implicated in EAE for the first time and many have previously been shown to play a role in antigen processing, inflammation, neuroprotection, or neurodegeneration.

| S-EPMC2430926 | biostudies-literature

Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis.

Project description:Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35-55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17?cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-?B nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17?cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS.

| S-EPMC6100297 | biostudies-literature

A method for histopathological study of the multifocal nature of spinal cord lesions in murine experimental autoimmune encephalomyelitis.

Project description:Experimental autoimmune encephalomyelitis (EAE) is a well-established mouse model for multiple sclerosis and is characterized by infiltration of mononuclear cells and demyelination within the central nervous system along with the clinical symptoms of paralysis. EAE is a multifocal and random disease, which sometimes makes histopathologic analysis of lesions difficult as it may not be possible to predict where lesions will occur, especially when evaluating cross sections of spinal cord. Consequently, lesions may be easily missed due to limited sampling in traditional approaches. To evaluate the entire length of the spinal cord while maintaining anatomic integrity, we have developed a method to section the cord within the decalcified spinal column, which allows for the study of the multifocal nature of this disease and also minimizes handling artifact. HE and Luxol fast blue staining of these spinal cord sections revealed a paucity of lesions in some areas, while others showed marked inflammation and demyelination. The percentage of spinal cord affected by EAE was evaluated at four separate areas of longitudinally sectioned cord and it varied greatly within each animal. Immunohistochemical staining of in situ spinal cords which had undergone decalcification was successful for key immuno-markers used in EAE research including CD3 for T cells, B220 for B cells and F4/80 for murine macrophages. This method will allow investigators to look at the entire spinal cord on a single slide and evaluate the spinal cord with and without classic EAE lesions.

| S-EPMC4741089 | biostudies-literature

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