ArticleActa neuropathologica2012
Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS.
Article in Acta neuropathologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
85 citing papers in PubMed, 138 citations in OpenAlex.
- Review
- Astrocyte-Specific Upregulation of Tumor Necrosis Factor Receptor II Ameliorates Pathological Phenotypes in APPNeuroscience bulletin · 2026Article
- Astrocyte Biology in CNS Inflammatory Diseases: A Clinical-Translational Perspective.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Astroglial TNFR2 signaling regulates hippocampal synaptic function and plasticity in a sex dependent manner.Brain, behavior, and immunity · 2025Article
- Upregulating mTOR/S6 K Pathway by CASTOR1 Promotes Astrocyte Proliferation and Myelination in GpamMolecular neurobiology · 2025Article
- Single intracerebroventricular TNFR2 agonist injection impacts remyelination in the cuprizone model.Journal of molecular medicine (Berlin, Germany) · 2025Article
- The Effect of Tumor Necrosis Factor-α and Interleu-Kin-1β on the Restorative Properties of Human Oligodendrocyte Precursor Cells In Vitro.Bioengineering (Basel, Switzerland) · 2025Article
- The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.Brain, behavior, & immunity - health · 2025Review
- Astrocytes in aging.Neuron · 2025Review
- TNFR2 signaling in oligodendrocyte precursor cells suppresses their immune-inflammatory function and detrimental microglia activation in CNS demyelinating disease.Brain, behavior, and immunity · 2025Article
- Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Immunity impacts cognitive deficits across neurological disorders.Journal of neurochemistry · 2024Review
- Interplay between androgen and CXCR4 chemokine signaling in myelin repair.Acta neuropathologica communications · 2024Article
- Astrocytes: Lessons Learned from the Cuprizone Model.International journal of molecular sciences · 2023Review
- The role of monocytes in optic nerve injury.Neural regeneration research · 2023Review
- Astrogliosis in multiple sclerosis and neuro-inflammation: what role for the notch pathway?Frontiers in immunology · 2023Review
- Upregulation of C-X-C motif chemokine 12 in the spinal cord alleviated the symptoms of experimental autoimmune encephalomyelitis in Lewis rats.Frontiers in neuroscience · 2023Article
- Sera of Neuromyelitis Optica Patients Increase BID-Mediated Apoptosis in Astrocytes.International journal of molecular sciences · 2022Article
- Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination with progressive failure of remyelination. Prior studies using murine models of MS indicate that remyelination within the adult central nervous system (CNS) requires the expression and activity of TNFR2 and CXCR4 by oligodendrocyte progenitor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes. Here, we extend these studies by examining the role of TNFR2 in the expression of the CXCR4 ligand, CXCL12, within the corpus callosum (CC) during cuprizone (CPZ) intoxication and by demonstrating that lentiviral-mediated gene delivery of CXCL12 to the demyelinated CC improves OPC proliferation and myelin expression during remyelination. Activated astrocytes and microglia express both TNFR1 and TNFR2 within the demyelinated CC. However, CPZ intoxicated TNFR2-/- mice exhibit loss of up-regulation of CXCL12 in astrocytes with concomitant decreases in numbers of CXCR4+ NG2+ OPCs within the CC. While CXCR4 antagonism does not affect OPC migration from subventricular zones into the CC, it decreases their proliferation and differentiation within the CC. Stereotactic delivery of lentivirus expressing CXCL12 protein into the CC of acutely demyelinated TNFR2-/- mice increases OPC proliferation and expression of myelin. In contrast, chronically demyelinated wild-type mice, which exhibit significant loss of astrocytes and OPCs, are unable to be rescued via CXCL12 lentivirus alone but instead required engraftment of CXCL12-expressing astrocytes for increased myelin expression. Our results show that TNFR2 activation induces CXCL12 expression in the demyelinated CC via autocrine signaling specifically within astrocytes, which promotes OPC proliferation and differentiation. In addition, gene delivery of critical pro-myelinating proteins might be a feasible approach for the treatment of remyelination failure in MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.