ArticlePloS one2011
Activated microglia inhibit axonal growth through RGMa.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
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- Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update.International journal of molecular sciences · 2025Review
- Netrin-1: Dual Roles in Neuroinflammation and Neurodegenerative Disease Dynamics.International journal of inflammation · 2025Review
- Current perspectives on microglia-neuron communication in the central nervous system: Direct and indirect modes of interaction.Journal of advanced research · 2024Review
- Astrocytes and microglia in the coordination of CNS development and homeostasis.Journal of neurochemistry · 2024Review
- Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion.Translational stroke research · 2024Article
- Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.Frontiers in immunology · 2024Article
- Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury.Neural regeneration research · 2023Article
- Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts.Frontiers in neurology · 2023Review
- Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult.Scientific reports · 2022Article
- Microglial control of neuronal development via somatic purinergic junctions.Cell reports · 2022Article
- Review
- Synaptic or Non-synaptic? Different Intercellular Interactions with Retinal Ganglion Cells in Optic Nerve Regeneration.Molecular neurobiology · 2022Review
- Microglia regulate chandelier cell axo-axonic synaptogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells.Frontiers in cell and developmental biology · 2022Article
- Repulsive guidance molecule acts in axon branching in Caenorhabditis elegans.Scientific reports · 2021Article
- Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes.Molecular neurobiology · 2021Review
- miR-106b-5p upregulation is associated with microglial activation and inflammation in the mouse hippocampus following status epilepticus.Experimental brain research · 2021Article
- Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
By causing damage to neural networks, spinal cord injuries (SCI) often result in severe motor and sensory dysfunction. Functional recovery requires axonal regrowth and regeneration of neural network, processes that are quite limited in the adult central nervous system (CNS). Previous work has shown that SCI lesions contain an accumulation of activated microglia, which can have multiple pathophysiological influences. Here, we show that activated microglia inhibit axonal growth via repulsive guidance molecule a (RGMa). We found that microglia activated by lipopolysaccharide (LPS) inhibited neurite outgrowth and induced growth cone collapse of cortical neurons in vitro--a pattern that was only observed when there was direct contact between microglia and neurons. After microglia were activated by LPS, they increased expression of RGMa; however, treatment with RGMa-neutralizing antibodies or transfection of RGMa siRNA attenuated the inhibitory effects of microglia on axonal outgrowth. Furthermore, minocycline, an inhibitor of microglial activation, attenuated the effects of microglia and RGMa expression. Finally, we examined whether these in vitro patterns could also be observed in vivo. Indeed, in a mouse SCI model, minocycline treatment reduced the accumulation of microglia and decreased RGMa expression after SCI, leading to reduced dieback in injured corticospinal tracts. These results suggest that activated microglia play a major role in inhibiting axon regeneration via RGMa in the injured CNS.
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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.