ArticleGlia2015
Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal β-oxidation deficiency.
Article in Glia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.Cell death & disease · 2026Article
- Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice.The Journal of clinical investigation · 2026Article
- Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.Frontiers in immunology · 2026Review
- Review
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 2025Review
- Article
- Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.Signal transduction and targeted therapy · 2021Article
- The potential roles of mJournal of neuroinflammation · 2021Article
- Exploring the VISTA of microglia: immune checkpoints in CNS inflammation.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms.Neuron · 2020Article
- Article
- Peroxisomes and Innate Immunity: Antiviral Response and Beyond.International journal of molecular sciences · 2019Review
- Microglia lacking a peroxisomal β-oxidation enzyme chronically alter their inflammatory profile without evoking neuronal and behavioral deficits.Journal of neuroinflammation · 2019Article
- Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures.EMBO reports · 2018Article
- Microglial signatures and their role in health and disease.Nature reviews. Neuroscience · 2018Review
- Autonomous Purkinje cell axonal dystrophy causes ataxia in peroxisomal multifunctional protein-2 deficiency.Brain pathology (Zurich, Switzerland) · 2018Article
- Letter to the Editor re: Increased Expression of Translocator Protein (TSPO) Marks Pro-inflammatory Microglia but Does Not Predict Neurodegeneration.Molecular imaging and biology · 2018Article
- Increased Expression of Translocator Protein (TSPO) Marks Pro-inflammatory Microglia but Does Not Predict Neurodegeneration.Molecular imaging and biology · 2018Article
- Microglia Express Mu Opioid Receptor: Insights From Transcriptomics and Fluorescent Reporter Mice.Frontiers in psychiatry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The functional diversity and molecular adaptations of reactive microglia in the chronically inflamed central nervous system (CNS) are poorly understood. We previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, persistently accumulate reactive myeloid cells in the gray matter of the CNS. Here, we show that the increased numbers of myeloid cells solely derive from the proliferation of resident microglia and not from infiltrating monocytes. We defined the signature of Mfp2(-/-) microglia by gene expression profiling after acute isolation, which was validated by quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric analysis. The features of Mfp2(-/-) microglia were compared with those from SOD1(G93A) mice, an amyotrophic lateral sclerosis model. In contrast to the neurodegenerative milieu of SOD1(G93A) spinal cord, neurons were intact in Mfp2(-/-) brain and Mfp2(-/-) microglia lacked signs of phagocytic and neurotoxic activity. The chronically reactive state of Mfp2(-/-) microglia was accompanied by the downregulation of markers that specify the unique microglial signature in homeostatic conditions. In contrast, mammalian target of rapamycin (mTOR) and downstream glycolytic and protein translation pathways were induced, indicative of metabolic adaptations. Mfp2(-/-) microglia were immunologically activated but not polarized to a pro- or anti-inflammatory phenotype. A peripheral lipopolysaccharide challenge provoked an exaggerated inflammatory response in Mfp2(-/-) brain, consistent with a primed state. Taken together, we demonstrate that chronic activation of resident microglia does not necessarily lead to phagocytosis nor overt neurotoxicity.
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What OpenQuestion holds
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.