Regulation of gene expression associated with acute experimental autoimmune encephalomyelitis by Lovastatin

2004 ◽  
Vol 77 (1) ◽  
pp. 63-81 ◽  
Author(s):  
Ajaib Singh Paintlia ◽  
Manjeet Kaur Paintlia ◽  
Avtar Kaur Singh ◽  
Romesh Stanislaus ◽  
Anne Genevieve Gilg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Regulation Of Gene Expression ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Patterns ◽  
Immune Functions ◽  
Autoimmune Encephalomyelitis ◽  
Transcriptional Changes ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Experimental Autoimmune

AbstractMicroglia 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.

CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis

2003 ◽  
Vol 73 (5) ◽  
pp. 667-678 ◽  
Author(s):  
Agata Matejuk ◽  
Corwyn Hopke ◽  
Jami Dwyer ◽  
Sandhya Subramanian ◽  
Richard E. Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Pattern ◽  
Gene Expression Pattern ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis

2021 ◽  
Author(s):  
Xiaomei Liu ◽  
Feng Zhou ◽  
Weixiao Wang ◽  
Guofang Chen ◽  
Qingxiu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Cytokines ◽  
Lentiviral Vector ◽  
Spinal Injury ◽  
Demyelinating Diseases ◽  
Autoimmune Encephalomyelitis ◽  
Aberrant Expression ◽  
Experimental Autoimmune

Abstract Background Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cells infiltration and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Here, we examined the effects of lncRNA Gm13568 (a co-upregulated lncRNA both in EAE mice and in mouse primary astrocytes activated by IL-9) on the activation of astrocytes and the process of EAE. Methods In vitro, shRNA-recombinant lentivirus with Glial fibrillary acidic protein (GFAP) promoter were performed to determine the relative gene expression and proinflammatory cytokines production in IL-9 treated-astrocytes using Western blot, real-time PCR and Cytometric bead array, respectively. RIP and ChIP assays were analyzed for the mechanism of lncRNA Gm13568 regulating gene expression. Immunofluorescence assays was performed to measure the protein expression in astrocytes. In vivo, H&E staining and LFB staining were applied to detect the inflammatory cells infiltrations and the medullary sheath damage in spinal cords of EAE mice infected by the recombinant lentivirus. Results were analyzed by one-way ANOVA or student’s t-test, as appropriate. Results Knockdown of the endogenous lncRNA Gm13568 remarkably inhibits the Notch1 expression, astrocytosis and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) as well as the production of inflammatory cytokines and chemokines (IL-6, TNF-α, IP-10) in IL-9 activated astrocytes. In which, Gm13568 associates with CBP/P300 is enriched in the promoter of Notch1 genes. More importantly, inhibiting Gm13568 with lentiviral vector in astrocytes ameliorates significantly inflammation and demyelination in EAE mice, therefore delaying the EAE process. Conclusions These findings uncover that Gm13568 regulates the production of inflammatory cytokines in active astrocytes and affects the pathogenesis of EAE through the Notch1/STAT3 pathway. LncRNA Gm13568 may be a promising target for treating MS and demyelinating diseases.

scholarly journals Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Marta Pulido-Salgado ◽  
Jose M. Vidal-Taboada ◽  
Gerardo Garcia Diaz-Barriga ◽  
Joan Serratosa ◽  
Tony Valente ◽  
...  
Keyword(s):  
Gene Expression ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

2020 ◽  
Author(s):  
Vittoria Borgonetti ◽  
Maria Domenica Sanna ◽  
Laura Lucarini ◽  
Nicoletta Galeotti
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Rna Binding ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Rna Binding Protein ◽  
Motor Dysfunction ◽  
Autoimmune Encephalomyelitis ◽  
Activated Microglia ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood–brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.

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