ArticleScientific reports2017
PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting enhancing myelin regeneration reverses cognitive deficits in a mouse model of intellectual disability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Ultrastructure of astrocytes using volume electron microscopy: A scoping review.The Journal of physiology · 2026Article
- Mechanism and application of immune interventions in intracerebral haemorrhage.Expert reviews in molecular medicine · 2024Review
- Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses.Glia · 2024Article
- The thrombin receptor (PAR1) is associated with microtubules, mitosis and process formation in glioma cells.Heliyon · 2024Article
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- Control of complex behavior by astrocytes and microglia.Neuroscience and biobehavioral reviews · 2022Review
- Estimating the glutamate transporter surface density in distinct sub-cellular compartments of mouse hippocampal astrocytes.PLoS computational biology · 2022Article
- Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity.International journal of molecular sciences · 2021Review
- The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells.Neural plasticity · 2021Article
- Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1.Cell reports · 2020Article
- Nanostructural Diversity of Synapses in the Mammalian Spinal Cord.Scientific reports · 2020Article
- Blocking the Thrombin Receptor Promotes Repair of Demyelinated Lesions in the Adult Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Neuron-generated thrombin induces a protective astrocyte response via protease activated receptors.Glia · 2020Article
- Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets.Journal of stroke · 2020Review
- Neuroprotection and vasculoprotection using genetically targeted protease-ligands.Brain research · 2019Article
- Podocalyxin is required for maintaining blood-brain barrier function during acute inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Thrombin and the Protease-Activated Receptor-1 in Organophosphate-Induced Status Epilepticus.Journal of molecular neuroscience : MN · 2019Article
- Thrombin contributes to the injury development and neurological deficit after acute subdural hemorrhage in rats only in collaboration with additional blood-derived factors.BMC neuroscience · 2018Article
- MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke.
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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.