ArticleThe Journal of clinical investigation2017
Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis.Frontiers in neuroscience · 2023Pooled it
- Article
- mTOR Activation Is Required for the Proliferation of Reactive Astrocytes in the Hippocampus During Traumatic Brain Injury.Biomolecules · 2026Article
- Involvement of trimethylamine N-oxide in major depressive disorder via astrocytic d-Serine dysregulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- A mitochondrial-neuroinflammation-D-serine connection in epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neurovascular coupling dysfunction of the frontal‒thalamic circuit in postconcussion syndrome.Brain imaging and behavior · 2026Article
- Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.Brain : a journal of neurology · 2026Article
- Glial D-serine modulates oligodendrocyte lineage progression under inflammatory conditions.Frontiers in cellular neuroscience · 2026Article
- Metabolomics of cerebrospinal fluid following traumatic brain injury: Exploration of biomarkers for secondary injuries and severity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Detection and functional assessment of D-amino acids as potential biomarkers in neurological disorders.Molecular biology reports · 2025Review
- Astrocyte-Neuron Metabolic Synergies in Neurological Homeostasis and Disease.Neurochemical research · 2025Review
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Contralateral Structure and Molecular Response to Severe Unilateral Brain Injury.Brain sciences · 2025Article
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Exploring Synaptic Pathways in Traumatic Brain Injury: A Cross-Phenotype Genomics Approach.Journal of neurotrauma · 2025Article
- The immunological landscape of traumatic brain injury: insights from pathophysiology to experimental models.Frontiers in neurology · 2025Review
- L-serine metabolic regulation and host respiratory homeostasis.Frontiers in cellular and infection microbiology · 2025Review
- Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases.Neurochemical research · 2024Review
- Chemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor.ACS medicinal chemistry letters · 2024Article
- Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
After traumatic brain injury (TBI), glial cells have both beneficial and deleterious roles in injury progression and recovery. However, few studies have examined the influence of reactive astrocytes in the tripartite synapse following TBI. Here, we have demonstrated that hippocampal synaptic damage caused by controlled cortical impact (CCI) injury in mice results in a switch from neuronal to astrocytic d-serine release. Under nonpathological conditions, d-serine functions as a neurotransmitter and coagonist for NMDA receptors and is involved in mediating synaptic plasticity. The phasic release of neuronal d-serine is important in maintaining synaptic function, and deficiencies lead to reductions in synaptic function and plasticity. Following CCI injury, hippocampal neurons downregulated d-serine levels, while astrocytes enhanced production and release of d-serine. We further determined that this switch in the cellular source of d-serine, together with the release of basal levels of glutamate, contributes to synaptic damage and dysfunction. Astrocyte-specific elimination of the astrocytic d-serine-synthesizing enzyme serine racemase after CCI injury improved synaptic plasticity, brain oscillations, and learning behavior. We conclude that the enhanced tonic release of d-serine from astrocytes after TBI underlies much of the synaptic damage associated with brain injury.
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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.