Integrative Transcriptomic Analysis Reveals Impaired Oligodendrocyte Maturation and Myelination Signature in the Hippocampus of a Murine Model of Neuropsychiatric Lupus

Integrated proteogenomic profiling reveals coordinated differential expression signatures during neuroinflammation.

BACKGROUND Experimental autoimmune encephalomyelitis (EAE) is a key model of autoimmune neuroinflammation, yet an integrated characterization of transcriptional and proteomic dysregulation of the CNS has been missing. METHODS In this study, we performed deep proteogenomic profiling of the spinal cord from mice induced with EAE during acute disease by combining RNA-seq (GEO, GSE330115) and LC-MS/MS (PRIDE, PXD078146). RESULTS We identified extensive upregulation of innate and adaptive immune response signatures alongside concordant downregulation of neuronal, synaptic, and mitochondrial pathways. Despite expected divergence as reported in previous studies discussing neuroinflammation models, log₂ fold changes and pathway enrichment scores showed high concordance between both gene product levels (Rp = 0.867, p < 2.2 × 10⁻1⁶, 95% CI [0.859, 0.874]). Loss of synaptic and metabolic integrity was predominantly observed at the protein level, whereas transcriptomics alone underestimated these structural deficits. In addition to inflammatory changes within CNS-resident cells during pathology analysis of markers typically absent in healthy CNS suggested that immune cell infiltration, in addition to pro-inflammatory phenotypic shifts of CNS-resident glial cells, accounts for the majority of non-CNS protein level changes in EAE, rather than passive plasma leakage. CONCLUSION Together, this integrated dataset reveals coordinated multilayer molecular remodelling in neuroinflammation and refines mechanistic interpretation of biomarker origin in inflamed CNS tissue in mice.

Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-Frontotemporal Dementia

SLC7A11-associated astrocyte states are linked to redox imbalance and synaptic microenvironment remodeling in multiple sclerosis: translational implications

Multiple sclerosis (MS) is characterized by inflammatory demyelination, oxidative stress, and neurological dysfunction. Despite disease-modifying therapies, chronic active lesions and ongoing neurodegeneration remain largely untreated, highlighting the need for mechanistically informed translational targets. We analyzed a human single-nucleus RNA-sequencing dataset (GSE279180) including healthy controls and MS samples. Astrocyte subpopulations were examined using reclustering, pseudotime inference, co-expression network analysis, SLC7A11-high/low stratification, virtual knockout prediction, and gene set enrichment analysis. Key findings were further assessed in vivo using a cuprizone-induced demyelination mouse model. Broad cellular remodeling was observed in MS lesions, including altered neuroactive ligand-receptor interactions, calcium signaling, glutamatergic synapse, and synaptic vesicle cycle-related pathways. SLC7A11 was enriched in astrocytes and increased along later pseudotime stages. SLC7A11-high astrocytes were linked to impaired antioxidant defense (GSH/GPX4) and synaptic vesicle-related remodeling. CPZ-treated mice showed decreased SLC7A11/GPX4 colocalization and increased SYP–GFAP colocalization, along with behavioral deficits, demyelination, and inflammatory-redox imbalance. SLC7A11-associated astrocyte states are associated with redox imbalance and synaptic microenvironment remodeling in MS. These states may inform future biomarker development and therapeutic investigation. Our findings provide a glial-state framework linking neuroinflammation, oxidative stress, and synaptic dysfunction, highlighting potential avenues for translational strategies in MS.

Oligodendrocyte Enriched Brain Organoids Reveal Impaired Oligodendroglial Maturation and Altered Neural Network Activity in Down Syndrome

It is shown that trisomy 21 disrupts early developmental stages and establish oligodendrocyte enriched brain organoids as a human model to investigate the developmental origins of white matter and network dysfunction in DS.

Characterization of Astrocyte Density in the Pitt–Hopkins Syndrome Mouse Model of Autism Spectrum Disorder

Germline heterozygous TCF4 LOF, which models PTHS, does not appear to significantly affect the astrocyte lineage at the cell population level, and germline heterozygous Tcf4 LOF did not result in misallocation of ventrally derived astrocytes into the dorsal cortex.

Oligodendroglial deletion of the microcephaly gene Cit-k disrupts cortical connectivity and cognitive function

It is shown that oligodendroglial Cit-k loss and the resulting hypomyelination are sufficient to produce long-lasting neurological and behavioral impairments independently of primary neuronal defects.