PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

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dc.citation.volume7
dc.contributor.authorSweeney, Amanda M.
dc.contributor.authorFleming, Kelsey E.
dc.contributor.authorMcCauley, John P.
dc.contributor.authorRodriguez, Marvin F.
dc.contributor.authorMartin, Elliot T.
dc.contributor.authorSousa, Alioscka A. [UNIFESP]
dc.contributor.authorLeapman, Richard D.
dc.contributor.authorScimemi, Annalisa
dc.coverageLondon
dc.date.accessioned2020-07-17T14:02:40Z
dc.date.available2020-07-17T14:02:40Z
dc.date.issued2017
dc.description.abstractThe 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.en
dc.description.affiliationSUNY Albany, Dept Biol, 1400 Washington Ave, Albany, NY 12222 USA
dc.description.affiliationSUNY Coll Oneonta, Dept Comp Sci, 9000 Rockville Pike, Oneonta, NY 13820 USA
dc.description.affiliationNatl Inst Biomed Imaging & Bioengineering, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20852 USA
dc.description.affiliationUniv Rochester Med Ctr, 77 Ridgeland Rd, Rochester, NY 14623 USA
dc.description.affiliationSUNY Coll Oneonta, IT Enterprise Applicat Serv, 108 Ravine Pkwy, Oneonta, NY 13820 USA
dc.description.affiliationUniv Fed Sao Paulo, Dept Biochem, Rua Tres Maio 100, BR-04044 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biochem, Rua Tres Maio 100, BR-04044 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSUNY Albany
dc.description.sponsorshipSUNY Albany Research Foundation
dc.description.sponsorshipSUNY Brain Network of Excellence
dc.description.sponsorshipIntramural Research Program of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/srep43606
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/srep43606
dc.identifier.fileWOS000396279600001.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54939
dc.identifier.wosWOS:000396279600001
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlePAR1 activation induces rapid changes in glutamate uptake and astrocyte morphologyen
dc.typeinfo:eu-repo/semantics/article
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