Cited by 586Barrier Structure and Function StudiesConnexins and lens biologyAdenosine and Purinergic Signaling

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Signaling at the Gliovascular Interface

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Simard, Marie, Arcuino, Gregory, Takano, Takahiro, Liu, Qing Song, Nedergaard, Maiken·2003·The Journal of Neuroscience

DOI 10.1523/jneurosci.23-27-09254.2003PMC PMC6740832

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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.

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Authors: Simard, M., Arcuino, G., Takano, T., Liu, Q. S., & Nedergaard, M.
Affiliations: New York Medical College (US)
ORCID: Takano, Takahiro
Nedergaard, Maiken
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2003-10-08
Volume: 23
Issue: 27
Pages: 9254-9262
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.23-27-09254.2003
PMC: PMC6740832
OpenAlex: W2105112166
Cited by: 586
References: 55
Citations by year: 2026: 6 · 2025: 16 · 2024: 17 · 2023: 19 · 2022: 14 · 2021: 24 · 2020: 20 · 2019: 18 · 2018: 16 · 2017: 30 · 2016: 26 · 2015: 45 · 2014: 26 · 2013: 36 · 2012: 41
FWCI: 17.36
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (7k08ns001672-06)
National Institute of Neurological Disorders and Stroke (NS38073, R01NS030007, R01NS038073, NS 30007, NS01672)
National Center for Research Resources (RR14661, S10RR014661)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords: astrocyte-neuron communication, calcium signaling, gap junctions, connexin 43, purinergic signaling, P2Y2 receptor, P2Y4 receptor, ATP, calcium waves, blood-brain barrier, brain endothelial cells, pericytes, blood flow regulation, water homeostasis
MeSH terms: Adenosine Triphosphate, Animals, Astrocytes, Basement Membrane, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Diffusion, Endothelium, Vascular, Fluorescent Dyes, Glial Fibrillary Acidic Protein, Male, Microcirculation, Rats, Sprague-Dawley, Gap Junctions, Connexin 43, Receptors, Purinergic P2, Patch-Clamp Techniques, Calcium Signaling, Pericytes, Rats, Receptors, Purinergic P2Y2, In Vitro Techniques

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