Remodeling of Neurotransmission and Chemokine Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus
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PROVIDER: PRJNA689211 | ENA |
REPOSITORIES: ENA
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Project description:Cognitive dysfunction and mood changes are prevalent and especially taxing issues to patients with systemic lupus erythematosus (SLE). TNF-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/lpr and MRL/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the PI3K-Akt pathway in the MRL/lpr lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and therefore promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.
2021-01-03 | GSE164140 | GEO
Project description:Remodeling of Mouse Hippocampus Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus
| PRJNA716684 | ENA
Project description:TNF-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the hippocampi of MRL/+, MRL/lpr and MRL/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on hippocampal gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the PI3K-Akt pathway in the MRL/lpr lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and therefore promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.
2021-03-24 | GSE169486 | GEO
Project description:Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/lpr (that manifest lupus-like phenotype) and MRL/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL/lpr lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.
| S-EPMC7916450 | biostudies-literature
Project description:IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus
| PRJNA1101018 | ENA
Project description:We profiled the whole transcriptomes of male and female rat hypothalamic paraventricular nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in rats prenatally exposed (G15) to betamethasone. Pups were treated with saline on days 13, 14 and 15. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in epileptic rats and recovery following various treatments. The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking. Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission.
2019-01-04 | GSE124613 | GEO
Project description:We profiled the whole transcriptomes of male and female rat hypothalamic paraventricular nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in autism. The rats were prenatally exposed (G15) to betamethasone followed by repeated adiministration of N-Methyl-D-Aspartic acid on postnatal days 12, 13 and 15 which triggered the infantile spasms and autism spectrum disease behavior. Pups were treated with saline on days 13, 14 and 15 prior to NMDA administration. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in autistic rats . The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking. Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics.
2019-03-12 | GSE128091 | GEO
Project description:We profiled the whole transcriptomes of male rat hypothalamic arcuate nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in epilepsy and recovery following different treatments. The rats were prenatally exposed (G15) to betamethasone (or just saline for control) followed by repeated adiministration of N-Methyl-D-Aspartic acid on postnatal days 12, 13 and 15 which triggered infantile spasms. Pups were treated with either ATCH, PMX53 (a potent C5ar1 antagonist) or saline to act as a control, on days 13, 14 and 15 prior to NMDA administration to determine what effects each treatment had on transcriptome recovery. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in epileptic rats and recovery following various treatments. The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking. Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics. However, ACTH treatment, which is effective in significantly improving seizure outcomes, recovered 49% of the normal transcriptome in the hypothalamic arcuate nucleus. Surprisingly, PMX53 treatment recovered 64% of the normal transcriptome despite having no significant effect on behavioural seizure outcomes.
2016-05-04 | GSE81061 | GEO
Project description:[Objectives]: Neuropsychiatric systemic lupus erythematosus (NPSLE) is often difficult to diagnose and distinguish from those of other diseases, because no specific antibodies have yet been detected. [Methods]: We developed a novel proteomic strategy for identifying and profiling antigens in immune complexes (ICs) in the cerebrospinal fluid (CSF) of 26 NPSLE patients. We performed in vitro experiments using astrocytes and analyzed functional change by microarray. [Results]: We identified ICs of suprabasin (SBSN), a molecule which is thought to play a role in epidermal differentiation. Microarray data showed that the senescence and autophagy pathways were significantly changed in astrocytes with anti-SBSN antibody exposure compared to normal immunoglobulin G (IgG) exposure. [Conclusions]: These findings indicate that SBSN could be a novel autoantibody for the evaluation of suspected NPSLE, and may help elucidate the pathogenesis underlying this disease. The cultured human astrocyte exposed to non IgG, control rabbit IgG and anti suprabasin antibodies with or without lipopolysaccharide (1μg/ml) for 24 h were collected for RNA isolation. We divided into the following 6 samples, Non IgG LPS(-), Non IgG LPS(+), Norm IgG LPS(-), Norm IgG LPS(+), SBSN LPS(-) and SBSN IgG LPS(+).
2016-09-01 | E-GEOD-79189 | biostudies-arrayexpress
Project description:[Objectives]: Neuropsychiatric systemic lupus erythematosus (NPSLE) is often difficult to diagnose and distinguish from those of other diseases, because no specific antibodies have yet been detected. [Methods]: We developed a novel proteomic strategy for identifying and profiling antigens in immune complexes (ICs) in the cerebrospinal fluid (CSF) of 26 NPSLE patients. We performed in vitro experiments using astrocytes and analyzed functional change by microarray. [Results]: We identified ICs of suprabasin (SBSN), a molecule which is thought to play a role in epidermal differentiation. Microarray data showed that the senescence and autophagy pathways were significantly changed in astrocytes with anti-SBSN antibody exposure compared to normal immunoglobulin G (IgG) exposure. [Conclusions]: These findings indicate that SBSN could be a novel autoantibody for the evaluation of suspected NPSLE, and may help elucidate the pathogenesis underlying this disease.
2016-09-01 | GSE79189 | GEO