ArticleJournal of neuroinflammation2017
Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Volume electron microscopy in axon regeneration research: insights into mitochondria, endoplasmic reticulum, and membrane contacts.Frontiers in neural circuits · 2026Review
- Sodium channel endocytosis drives axon initial segment plasticity.Science advances · 2023Article
- Adult-onset depletion of sulfatide leads to axonal degeneration with relative myelin sparing.Glia · 2023Article
- Three-dimensional ultrastructure analysis of organelles in injured motor neuron.Anatomical science international · 2023Review
- Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion.Biomedicines · 2023Article
- Alzheimer's disease: an axonal injury disease?Frontiers in aging neuroscience · 2023Review
- Lysophosphatidic acid signaling via LPAJournal of neurochemistry · 2022Article
- Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development.Frontiers in cellular neuroscience · 2022Article
- Brain region-specific microglial and astrocytic activation in response to systemic lipopolysaccharides exposure.Frontiers in aging neuroscience · 2022Article
- Pathophysiological Roles of Abnormal Axon Initial Segments in Neurodevelopmental Disorders.Cells · 2021Review
- Early Adolescence Prefrontal Cortex Alterations in Female Rats Lacking Dopamine Transporter.Biomedicines · 2021Article
- Trafficking mechanisms underlying NaChannels (Austin, Tex.) · 2020Review
- Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.BMC pediatrics · 2020Article
- Microglial process convergence on axonal segments in health and disease.Neuroimmunology and neuroinflammation · 2020Article
- The interaction of ceramide 1-phosphate with group IVA cytosolic phospholipase AScience signaling · 2019Article
- RvD1binding with FPR2 attenuates inflammation via Rac1/NOX2 pathway after neonatal hypoxic-ischemic injury in rats.Experimental neurology · 2019Article
- Expression of a Fragment of Ankyrin 2 Disrupts the Structure of the Axon Initial Segment and Causes Axonal Degeneration in Drosophila.Molecular neurobiology · 2019Article
- Maturation Dynamics of the Axon Initial Segment (AIS) of Newborn Dentate Granule Cells in Young Adult C57BL/6J Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The Axon Initial Segment: An Updated Viewpoint.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner.
methodsC57BL/6J and NOX2
resultsLPS-induced neuroinflammation, characterized by enhanced microglial inflammation and increased expression of ROS-producing enzymes, altered AIS protein clustering. Importantly, inflammation-induced AIS changes were reversed following resolution of microglial inflammation. Modulation of the inflammatory response using anti-inflammatory Didox, even after significant AIS disruption occurred, increased the rate of AIS recovery. qPCR and IHC analysis revealed that expression of microglial NOX2, a ROS-producing enzyme, was significantly increased correlating with AIS disruption. Furthermore, ablation of NOX2 prevented inflammation-induced AIS plasticity, suggesting that ROS drive AIS structural plasticity.
conclusionsIn the presence of acute microglial inflammation, the AIS undergoes an adaptive change that is capable of spontaneous recovery. Moreover, recovery can be therapeutically accelerated. Together, these findings underscore the dynamic capabilities of this domain in the presence of a pathological insult and provide evidence that the AIS is a viable therapeutic target.
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