ArticleProceedings of the National Academy of Sciences of the United States of America2020
Oligodendroglial connexin 47 regulates neuroinflammation upon autoimmune demyelination in a novel mouse model of multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- The glia-immune network: Astrocytes and oligodendrocytes as microglial co-ordinators in health and disease.The Journal of physiology · 2026Review
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Cx47 Phosphorylation Exacerbates White Matter Damage and Kainic Acid Induced Epilepsy.CNS neuroscience & therapeutics · 2025Article
- Acupuncture regulates astrocyte neurotoxic polarization to protect blood-brain barrier integrity in delayed thrombolysis through mediating ERK1/2/Cx43 axis.IBRO neuroscience reports · 2025Article
- Microglia/Macrophages in Autoimmune Demyelinating Encephalomyelitis (Multiple Sclerosis/Neuromyelitis Optica).International journal of molecular sciences · 2025Review
- Identification of biomarkers associated with M1 macrophages in the ST-segment elevation myocardial infarction through bioinformatics and machine learning approaches.Scientific reports · 2025Article
- Neurotropic Murine β-Coronavirus Infection Causes Differential Expression of Connexin 47 in Oligodendrocyte Subpopulations Associated with Demyelination.Molecular neurobiology · 2025Article
- Blood exosome connexins and small RNAs related to demyelinating disease activity.Annals of clinical and translational neurology · 2025Article
- Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis.International journal of molecular sciences · 2024Review
- Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model.Scientific reports · 2024Article
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- Connexins Control Glial Inflammation in Various Neurological Diseases.International journal of molecular sciences · 2023Review
- Article
- Interactions Between Astrocytes and Oligodendroglia in Myelin Development and Related Brain Diseases.Neuroscience bulletin · 2023Review
- Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis.Nature communications · 2022Article
- GJA1/CX43 High Expression Levels in the Cervical Spinal Cord of ALS Patients Correlate to Microglia-Mediated Neuroinflammatory Profile.Biomedicines · 2022Article
- Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice.Protein & cell · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In multiple sclerosis plaques, oligodendroglial connexin (Cx) 47 constituting main gap junction channels with astroglial Cx43 is persistently lost. As mice with Cx47 single knockout exhibit no demyelination, the roles of Cx47 remain undefined. We aimed to clarify the effects of oligodendroglia-specific Cx47 inducible conditional knockout (icKO) on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein peptide (MOG35-55) in PLP/CreERT;Cx47fl/fl mice at 14 d after tamoxifen injection. Cx47 icKO mice demonstrated exacerbation of acute and chronic relapsing EAE with more pronounced demyelination than Cx47 flox (fl)/fl littermates. CD3+ T cells more abundantly infiltrated the spinal cord in Cx47 icKO than in Cx47 fl/fl mice throughout the acute to chronic phases. CXCR3-CCR6+CD4+ and IL17+IFNγ-CD4+ helper T (Th) 17 cells isolated from spinal cord and brain tissues were significantly increased in Cx47 icKO mice compared with Cx47 fl/fl mice, while MOG35-55-specific proliferation and proinflammatory cytokine production of splenocytes were unaltered. Microarray analysis of isolated microglia revealed stronger microglial activation toward proinflammatory and injury-response phenotypes with increased expressions of chemokines that can attract Th17 cells, including Ccl2, Ccl3, Ccl4, Ccl7, and Ccl8, in Cx47 icKO mice compared with Cx47 fl/fl mice. In Cx47 icKO mice, NOS2+ and MHC class II+ microglia were more enriched immunohistochemically, and A1-specific astroglial gene expressions and astroglia immunostained for C3, a representative A1 astrocyte marker, were significantly increased at the acute phase, compared with Cx47 fl/fl mice. These findings suggest that oligodendroglia-specific Cx47 ablation induces severe inflammation upon autoimmune demyelination, underscoring a critical role for Cx47 in regulating neuroinflammation.
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