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Publication : Astrocytic GPCR-Induced Ca(2+) Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes.

First Author  Ozawa K Year  2023
Journal  Int J Mol Sci Volume  24
Issue  17 PubMed ID  37686396
Mgi Jnum  J:340319 Mgi Id  MGI:7527596
Doi  10.3390/ijms241713590 Citation  Ozawa K, et al. (2023) Astrocytic GPCR-Induced Ca(2+) Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes. Int J Mol Sci 24(17)
abstractText  Activation of Gq-type G protein-coupled receptors (GPCRs) gives rise to large cytosolic Ca(2+) elevations in astrocytes. Previous in vitro and in vivo studies have indicated that astrocytic Ca(2+) elevations are closely associated with diameter changes in the nearby blood vessels, which astrocytes enwrap with their endfeet. However, the causal relationship between astrocytic Ca(2+) elevations and blood vessel diameter changes has been questioned, as mice with diminished astrocytic Ca(2+) signaling show normal sensory hyperemia. We addressed this controversy by imaging cortical vasculature while optogenetically elevating astrocyte Ca(2+) in a novel transgenic mouse line, expressing Opto-Gq-type GPCR Optoalpha1AR (Astro-Optoalpha1AR) in astrocytes. Blue light illumination on the surface of the somatosensory cortex induced Ca(2+) elevations in cortical astrocytes and their endfeet in mice under anesthesia. Blood vessel diameter did not change significantly with Optoalpha1AR-induced Ca(2+) elevations in astrocytes, while it was increased by forelimb stimulation. Next, we labeled blood plasma with red fluorescence using AAV8-P3-Alb-mScarlet in Astro-Optoalpha1AR mice. We were able to identify arterioles that display diameter changes in superficial areas of the somatosensory cortex through the thinned skull. Photo-stimulation of astrocytes in the cortical area did not result in noticeable changes in the arteriole diameters compared with their background strain C57BL/6. Together, compelling evidence for astrocytic Gq pathway-induced vasodiameter changes was not observed. Our results support the notion that short-term (<10 s) hyperemia is not mediated by GPCR-induced astrocytic Ca(2+) signaling.
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