ArticleCell death & disease2010
CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival.
Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Age-dependent effects of chronic traumatic and social isolation stress on mice social behavior.Neurobiology of stress · 2026Article
- The chemokine Cxcl14 regulates interneuron differentiation in layer I of the somatosensory cortex.Cell reports · 2024Article
- Tonic Activation of NR2D-Containing NMDARs Exacerbates Dopaminergic Neuronal Loss in MPTP-Injected Parkinsonian Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury.Neuron · 2022Article
- Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells.Translational psychiatry · 2022Review
- Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior.Pharmacological reports : PR · 2021Review
- Repetitive transcranial magnetic stimulation increases neurological function and endogenous neural stem cell migration via the SDF-1α/CXCR4 axis after cerebral infarction in rats.Experimental and therapeutic medicine · 2021Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Article
- Opioid and chemokine regulation of cortical synaptodendritic damage in HIV-associated neurocognitive disorders.Brain research · 2019Review
- Microglia Mediate HIV-1 gp120-Induced Synaptic Degeneration in Spinal Pain Neural Circuits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Novel Positive Allosteric Modulators of Glutamate Transport Have Neuroprotective Properties in an in Vitro Excitotoxic Model.ACS chemical neuroscience · 2019Article
- The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway.Cardiovascular diabetology · 2018Article
- The Cytokine CXCL12 Promotes Basket Interneuron Inhibitory Synapses in the Medial Prefrontal Cortex.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- HIV-associated synaptic degeneration.Molecular brain · 2017Review
- CXCR4 and NMDA Receptors Are Functionally Coupled in Rat Hippocampal Noradrenergic and Glutamatergic Nerve Endings.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Article
- Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.Frontiers in molecular neuroscience · 2016Article
- Induction of Interleukin-1β by Human Immunodeficiency Virus-1 Viral Proteins Leads to Increased Levels of Neuronal Ferritin Heavy Chain, Synaptic Injury, and Deficits in Flexible Attention.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repressor protein Rb, which is involved in the recruitment of chromatin modifiers (such as histone deacetylases (HDACs)) to gene promoters. In neurons, Rb controls activity-dependent genes essential to neuronal plasticity and survival, such as the N-methyl-D-aspartic acid (NMDA) receptor's subunit NR2B, the expression of which in the tetrameric ion channel largely affects calcium signaling by glutamate. In this study, we report that CXCL12 differentially modulates intracellular responses after stimulation of synaptic and extrasynaptic NMDA receptors, by a specific regulation of the NR2B gene that involves HDACs. Our results show that CXCL12 selectively inhibits NR2B expression in vitro and in vivo altering NMDA-induced calcium responses associated with neuronal death, while promoting prosurvival pathways that depend on stimulation of synaptic receptors. Along with previous studies, these findings underline the role of CXCL12/CXCR4 in the regulation of crucial components of glutamatergic transmission. These novel effects of CXCL12 may be involved in the physiological function of the chemokine in both developing and mature brains.
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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.