ArticleThe Journal of clinical investigation2020
Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
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- Astrocytic VPS35 coordinates iron homeostasis with HIF1α-VEGFa signaling to prevent astrocytic ferroptosis and to promote neocortical angiogenesis.Cell & bioscience · 2026Article
- Strategies for blood-brain barrier rejuvenation and repair.Nature reviews. Drug discovery · 2026Review
- Targeting the Microglia-Astrocyte OSM-OSMR Axis Restores Blood-Brain Barrier Integrity After Experimental Cerebral Ischemia-Reperfusion in Mice.Molecular neurobiology · 2026Article
- Endothelialized human umbilical cord mesenchymal stem cell-derived exosomes enhances angiogenesis and stabilizes the blood-spinal cord barrier after spinal cord injury.Journal of nanobiotechnology · 2026Article
- Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex.Cell death and differentiation · 2026Article
- The regenerative period of somatosensory nerves is closed by a DCC signaling axis.PLoS genetics · 2026Article
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- Astrocytic Netrin-1 modulates stress-induced anxiety susceptibility in mice through ADAM17-mediated TNFα shedding.Journal of neuroinflammation · 2026Article
- Serum proteomics reveals biomarkers for diagnosis, stratification, and mechanistic insights into cerebral microbleeds.Frontiers in aging neuroscience · 2026Article
- Effects of senescence on astrocyte to brain endothelial cell signaling.Neuroprotection (Chichester, England) · 2025Article
- Hepcidin depending on astrocytic NEO1 ameliorates blood-brain barrier dysfunction after subarachnoid hemorrhage.Cell death & disease · 2024Article
- Netrin-1-engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair.Science advances · 2024Article
- Astrocytes dynamically regulate the blood-brain barrier in the healthy brain.Neural regeneration research · 2024Article
- Article
- Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Attenuation of Alzheimer's brain pathology in 5XFAD mice by PTHAlzheimer's research & therapy · 2023Article
- Diverse roles for axon guidance pathways in adult tissue architecture and function.Natural sciences (Weinheim, Germany) · 2022Article
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- A novel spinal neuron connection for heat sensation.Neuron · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Astrocytes have multiple functions in the brain, including affecting blood vessel (BV) homeostasis and function. However, the underlying mechanisms remain elusive. Here, we provide evidence that astrocytic neogenin (NEO1), a member of deleted in colorectal cancer (DCC) family netrin receptors, is involved in blood vessel homeostasis and function. Mice with Neo1 depletion in astrocytes exhibited clustered astrocyte distribution and increased BVs in their cortices. These BVs were leaky, with reduced blood flow, disrupted vascular basement membranes (vBMs), decreased pericytes, impaired endothelial cell (EC) barrier, and elevated tip EC proliferation. Increased proliferation was also detected in cultured ECs exposed to the conditioned medium (CM) of NEO1-depleted astrocytes. Further screening for angiogenetic factors in the CM identified netrin-1 (NTN1), whose expression was decreased in NEO1-depleted cortical astrocytes. Adding NTN1 into the CM of NEO1-depleted astrocytes attenuated EC proliferation. Expressing NTN1 in NEO1 mutant cortical astrocytes ameliorated phenotypes in blood-brain barrier (BBB), EC, and astrocyte distribution. NTN1 depletion in astrocytes resulted in BV/BBB deficits in the cortex similar to those in Neo1 mutant mice. In aggregate, these results uncovered an unrecognized pathway, astrocytic NEO1 to NTN1, not only regulating astrocyte distribution, but also promoting cortical BV homeostasis and function.
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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.