%0 Journal Article %1 Stobart:2013:Proc-Natl-Acad-Sci-U-S-A:23386721 %A Stobart, J L %A Lu, L %A Anderson, H D %A Mori, H %A Anderson, C M %D 2013 %J Proc Natl Acad Sci U S A %K astrocytes central_nervous_system glial_cells neurovascular_system %N 8 %P 3149-3154 %R 10.1073/pnas.1215929110 %T Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase %U http://www.ncbi.nlm.nih.gov/pubmed/?term=23386721 %V 110 %X Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca(2+) produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling.

@article{Stobart:2013:Proc-Natl-Acad-Sci-U-S-A:23386721, abstract = {Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca(2+) produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling.}, added-at = {2013-05-07T19:53:33.000+0200}, author = {Stobart, J L and Lu, L and Anderson, H D and Mori, H and Anderson, C M}, biburl = {https://www.bibsonomy.org/bibtex/28596fb0d8860191eda46bd9d024ee41a/iskanbasal}, description = {Astrocyte-induced cortical vasodila... [Proc Natl Acad Sci U S A. 2013] - PubMed - NCBI}, doi = {10.1073/pnas.1215929110}, interhash = {b0085bc0750076981e4aca047d8466ad}, intrahash = {8596fb0d8860191eda46bd9d024ee41a}, journal = {Proc Natl Acad Sci U S A}, keywords = {astrocytes central_nervous_system glial_cells neurovascular_system}, month = feb, number = 8, pages = {3149-3154}, pmid = {23386721}, timestamp = {2013-05-07T19:53:33.000+0200}, title = {Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase}, url = {http://www.ncbi.nlm.nih.gov/pubmed/?term=23386721}, volume = 110, year = 2013 }