ArticlePloS one2017
The adenosine generating enzymes CD39/CD73 control microglial processes ramification in the mouse brain.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- The mechanism of different microglial receptors mediating central inflammation in chronic migraine: a meta-analysis.The journal of headache and pain · 2026Pooled it
- Heart failure-induced reprogramming of salt-evoked neurovascular coupling in the rat hypothalamus.The Journal of physiology · 2026Article
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Differential expression, activity, and fibroblast growth factor 2-mediated modulation of purine-metabolizing enzymes in cultured cortical astrocytes and microglia.Purinergic signalling · 2026Article
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- The myofascial rheostat: hyaluronan molecular weight dynamics and purinergic signalling as a physiological feedback system.Frontiers in physiology · 2026Review
- Dual CD73/AFrontiers in pharmacology · 2026Article
- Caffeine attenuates cisplatin induced microglial reactivity and cognitive dysfunction.Frontiers in molecular neuroscience · 2026Article
- The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.Frontiers in cell and developmental biology · 2026Review
- The metabolic engine of cognition: microglia-neuron interactions in health, ageing and disease.Nature metabolism · 2025Review
- Adenosine in the Brain: Recent Progress on Detection, Function, and Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- How microglia contribute to the induction and maintenance of neuropathic pain.Nature reviews. Neuroscience · 2025Review
- Article
- Extracellular adenosine oppositely regulates the purinome machinery in glioblastoma and mesenchymal stem cells.IUBMB life · 2024Article
- Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling.Nature communications · 2024Article
- ER and SOCE CaCell calcium · 2024Article
- A glia-enriched stem cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis.Cell reports. Medicine · 2024Article
- Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices.Nature communications · 2024Article
- Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling.bioRxiv : the preprint server for biology · 2024Article
- Neuropathological changes in the TASTPM mouse model of Alzheimer's disease and their relation to hyperexcitability and cortical spreading depolarization.Scientific reports · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglial cells invade the brain as amoeboid precursors and acquire a highly ramified morphology in the postnatal brain. Microglia express all essential purinergic elements such as receptors, nucleoside transporters and ecto-enzymes, including CD39 (NTPDase1) and CD73 (5'-nucleotidase), which sequentially degrade extracellular ATP to adenosine. Here, we show that constitutive deletion of CD39 and CD73 or both caused an inhibition of the microglia ramified phenotype in the brain with a reduction in the length of processes, branching frequency and number of intersections with Sholl spheres. In vitro, unlike wild-type microglia, cd39-/- and cd73-/- microglial cells were less complex and did not respond to ATP with the transformation into a more ramified phenotype. In acute brain slices, wild-type microglia retracted approximately 50% of their processes within 15 min after slicing of the brain, and this phenomenon was augmented in cd39-/- mice; moreover, the elongation of microglial processes towards the source of ATP or towards a laser lesion was observed only in wild-type but not in cd39-/- microglia. An elevation of extracellular adenosine 1) by the inhibition of adenosine transport with dipyridamole, 2) by application of exogenous adenosine or 3) by degradation of endogenous ATP/ADP with apyrase enhanced spontaneous and ATP-induced ramification of cd39-/- microglia in acute brain slices and facilitated the transformation of cd39-/- and cd73-/- microglia into a ramified process-bearing phenotype in vitro. These data indicate that under normal physiological conditions, CD39 and CD73 nucleotidases together with equilibrative nucleoside transporter 1 (ENT1) control the fate of extracellular adenosine and thereby the ramification of microglial processes.
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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.