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Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback.
- Source :
- Cell Reports; Aug2021, Vol. 36 Issue 5, pN.PAG-N.PAG, 1p
- Publication Year :
- 2021
-
Abstract
- Very-low-frequency oscillations in microvascular diameter cause fluctuations in oxygen delivery that are important for fueling the brain and for functional imaging. However, little is known about how the brain regulates ongoing oscillations in cerebral blood flow. In mouse and rat cortical brain slice arterioles, we find that selectively enhancing tone is sufficient to recruit a TRPV4-mediated Ca<superscript>2+</superscript> elevation in adjacent astrocyte endfeet. This endfoot Ca<superscript>2+</superscript> signal triggers COX-1-mediated "feedback vasodilators" that limit the extent of evoked vasoconstriction, as well as constrain fictive vasomotion in slices. Astrocyte- Ptgs1 knockdown in vivo increases the power of arteriole oscillations across a broad range of very low frequencies (0.01–0.3 Hz), including ultra-slow vasomotion (∼0.1 Hz). Conversely, clamping astrocyte Ca<superscript>2+</superscript> in vivo reduces the power of vasomotion. These data demonstrate bidirectional communication between arterioles and astrocyte endfeet to regulate oscillatory microvasculature activity. [Display omitted] • Arteriole tone increases astrocyte endfoot Ca<superscript>2+</superscript> via TRPV4 channels to engage COX-1 • COX-1 generates feedback dilators to limit the extent of constriction • Astrocytic COX-1 constrains ultra-slow arteriole oscillations in slice and in vivo • Clamping astrocyte Ca<superscript>2+</superscript> in vivo decreases cerebral vasomotion Haidey et al. find that arteriole constriction increases astrocyte endfoot Ca<superscript>2+</superscript> via TRPV4 channels to engage a COX-1 negative feedback signal that limits the degree of vasoconstriction. In vivo , astrocyte COX-1 constrains very-low-frequency oscillations (0.01–0.3 Hz) in arteriole diameter, while rhythmic fluctuations are reduced by clamping astrocyte Ca<superscript>2+</superscript>. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 26391856
- Volume :
- 36
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- 151702887
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109405