ArticleThe Journal of clinical investigation2005
Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
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- Hybrid Amyloid Quantum Dot Nano-Bio Assemblies to Probe Neuroinflammatory Damage.ACS chemical neuroscience · 2024Article
- Infectious Diseases.Advances in neurobiology · 2024Review
- Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Blood-Brain Barrier Damage Relevant to NeuroCOVID Brain Inflammation.ACS applied nano materials · 2023Article
- HIV-1 Tat reduces apical dendritic spine density throughout the trisynaptic pathway in the hippocampus of male transgenic mice.Neuroscience letters · 2022Article
- Transcriptomic Analysis ofFrontiers in psychiatry · 2019Article
- Scaling Synapses in the Presence of HIV.Neurochemical research · 2019Review
- Human immunodeficiency virus type 1 (HIV-1)-mediated neuroinflammation dysregulates neurogranin and induces synaptodendritic injury.Journal of neuroinflammation · 2018Article
- Temporal/compartmental changes in viral RNA and neuronal injury in a primate model of NeuroAIDS.PloS one · 2018Article
- Macrophages and Phospholipases at the Intersection between Inflammation and the Pathogenesis of HIV-1 Infection.International journal of molecular sciences · 2017Review
- Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury.Scientific reports · 2017Article
- Time-Dependent, HIV-Tat-Induced Perturbation of Human NeuronsFrontiers in molecular neuroscience · 2017Article
- Platelet-activating factor attenuation of long-term potentiation in rat hippocampal slices via protein tyrosine kinase signaling.Neuroscience letters · 2016Article
- Platelet-Activating Factor Receptors Mediate Excitatory Postsynaptic Hippocampal Injury in Experimental Autoimmune Encephalomyelitis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Hearing Loss After Activation of Hearing Preservation Cochlear Implants Might Be Related to Afferent Cochlear Innervation Injury.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2015Article
- α-Synuclein-induced synapse damage in cultured neurons is mediated by cholesterol-sensitive activation of cytoplasmic phospholipase A2.Biomolecules · 2015Article
- Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation.Frontiers in cellular neuroscience · 2015Article
- Neurotrophin strategies for neuroprotection: are they sufficient?Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Review
- The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Synaptic dysfunction in the hippocampus accompanies learning and memory deficits in human immunodeficiency virus type-1 Tat transgenic mice.Biological psychiatry · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neurologic impairment in HIV-1-associated dementia (HAD) and other neuroinflammatory diseases correlates with injury to dendrites and synapses, but how such injury occurs is not known. We hypothesized that neuroinflammation makes dendrites susceptible to excitotoxic injury following synaptic activity. We report that platelet-activating factor, an inflammatory phospholipid that mediates synaptic plasticity and neurotoxicity and is dramatically elevated in the brain during HAD, promotes dendrite injury following elevated synaptic activity and can replicate HIV-1-associated dendritic pathology. In hippocampal slices exposed to a stable platelet-activating factor analogue, tetanic stimulation that normally induces long-term synaptic potentiation instead promoted development of calcium- and caspase-dependent dendritic beading. Chemical preconditioning with diazoxide, a mitochondrial ATP-sensitive potassium channel agonist, prevented dendritic beading and restored long-term potentiation. In contrast to models invoking excessive glutamate release, these results suggest that physiologic synaptic activity may trigger excitotoxic dendritic injury during chronic neuroinflammation. Furthermore, preconditioning may represent a novel therapeutic strategy for preventing excitotoxic injury while preserving physiologic plasticity.
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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.