PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

Author Sweeney, Amanda M. Google Scholar
Fleming, Kelsey E. Google Scholar
McCauley, John P. Google Scholar
Rodriguez, Marvin F. Google Scholar
Martin, Elliot T. Google Scholar
Sousa, Alioscka A. Autor UNIFESP Google Scholar
Leapman, Richard D. Google Scholar
Scimemi, Annalisa Google Scholar
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.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor SUNY Albany
SUNY Albany Research Foundation
SUNY Brain Network of Excellence
Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health
Date 2017
Published in Scientific Reports. London, v. 7, p. -, 2017.
ISSN 2045-2322 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000396279600001

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