星形胶质细胞通过拉伸介导的 TRPV4-COX-1 反馈调节超慢动脉小动脉的波动。
Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback.
机构信息
Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physics and Astronomy, Faculty of Science, University of Calgary, Calgary, AB T2N 1N4, Canada.
出版信息
Cell Rep. 2021 Aug 3;36(5):109405. doi: 10.1016/j.celrep.2021.109405.
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 elevation in adjacent astrocyte endfeet. This endfoot Ca 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 Cain vivo reduces the power of vasomotion. These data demonstrate bidirectional communication between arterioles and astrocyte endfeet to regulate oscillatory microvasculature activity.
微动脉直径的极低频震荡会引起氧输送的波动，这对于为大脑提供燃料和进行功能成像很重要。然而，人们对大脑如何调节脑血流的持续震荡知之甚少。在小鼠和大鼠皮质脑片的小动脉中，我们发现选择性增强张力足以招募 TRPV4 介导的 Ca 升高在相邻星形胶质细胞足突中。该足突 Ca 信号触发 COX-1 介导的“反馈血管扩张剂”，限制诱发的血管收缩程度，并限制切片中的虚构血管运动。体内的星形胶质细胞-Ptgs1 敲低会增加广泛的极低频（0.01-0.3 Hz）的动脉震荡的功率，包括超慢血管运动（~0.1 Hz）。相反，体内钳制星形胶质细胞 Ca 会降低血管运动的功率。这些数据表明，小动脉和星形胶质细胞足突之间存在双向通讯，以调节震荡性微血管活动。
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