title: Signaling at the gliovascular interface.
abstract: Advances in fluorescent calcium indicating dyes over the past decade have identified calcium signaling as the tool by which astrocytes communicate among themselves and with neighboring neurons. Studies of astrocyte-neuron interactions have shown that calcium signaling is a potent modulator of the strength of both excitatory and inhibitory synapses. The concept that astrocytes possess a mechanism for rapid cell communication has not been incorporated, however, into the supportive functions of astrocytes. Because many of the classical tasks of astrocytes are linked to the blood-brain barrier, we have here examined the expression of proteins required for calcium signaling in their vascular end-foot processes. The gap junction protein, Cx43, was expressed intensively around the vessels interconnecting astrocytic end-foot processes. These gap junctions permitted diffusion of Lucifer yellow, specifically along the path of glial end feet apposed to the vessel wall. The purinergic receptors, P2Y(2) and P2Y(4), were also strongly expressed at the gliovascular interface and colocalized with GFAP around larger vessels in cortex. Multiphoton imaging of freshly prepared brain slices loaded with Fluo-4/AM revealed that ATP mobilized cytosolic calcium in astrocytic end feet, whereas electrical stimulation triggered calcium waves propagating along the vessel wall. Brain endothelial cells and pericytes were physically separated from astrocytes by the basal lamina and responded only weakly to ATP. These observations identify astrocytic end-foot processes plastered at the vessel wall as a center for purinergic signaling. It is speculated that calcium signaling may play a role in astrocytic functions related to the blood-brain barrier, including blood flow regulation, metabolic trafficking, and water homeostasis.
authors.affiliation: Department of Neurosurgery, New York Medical College, Valhalla, New York 10590, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Simard
authors.forename: Gregory
authors.initials: G
authors.lastname: Arcuino
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Qing Song
authors.initials: QS
authors.lastname: Liu
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001485:Basement Membrane / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation; D018031:Connexin 43 / Q000096:biosynthesis; D004058:Diffusion; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000166:cytology; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis; D058473:Receptors, Purinergic P2Y2
chemical_list: D018031:Connexin 43; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; D000255:Adenosine Triphosphate