Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes. / Ozawa, Katsuya; Nagao, Masaki; Konno, Ayumu; Iwai, Youichi; Vittani, Marta; Kusk, Peter; Mishima, Tsuneko; Hirai, Hirokazu; Nedergaard, Maiken; Hirase, Hajime.

In: International Journal of Molecular Sciences, Vol. 24, No. 17, 13590, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ozawa, K, Nagao, M, Konno, A, Iwai, Y, Vittani, M, Kusk, P, Mishima, T, Hirai, H, Nedergaard, M & Hirase, H 2023, 'Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes', International Journal of Molecular Sciences, vol. 24, no. 17, 13590. https://doi.org/10.3390/ijms241713590

APA

Ozawa, K., Nagao, M., Konno, A., Iwai, Y., Vittani, M., Kusk, P., Mishima, T., Hirai, H., Nedergaard, M., & Hirase, H. (2023). Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes. International Journal of Molecular Sciences, 24(17), [13590]. https://doi.org/10.3390/ijms241713590

Vancouver

Ozawa K, Nagao M, Konno A, Iwai Y, Vittani M, Kusk P et al. Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes. International Journal of Molecular Sciences. 2023;24(17). 13590. https://doi.org/10.3390/ijms241713590

Author

Ozawa, Katsuya ; Nagao, Masaki ; Konno, Ayumu ; Iwai, Youichi ; Vittani, Marta ; Kusk, Peter ; Mishima, Tsuneko ; Hirai, Hirokazu ; Nedergaard, Maiken ; Hirase, Hajime. / Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes. In: International Journal of Molecular Sciences. 2023 ; Vol. 24, No. 17.

Bibtex

@article{9a6d4e866bbb4e5ebc84a322476e67b3,
title = "Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes",
abstract = "Activation of Gq-type G protein-coupled receptors (GPCRs) gives rise to large cytosolic Ca2+ elevations in astrocytes. Previous in vitro and in vivo studies have indicated that astrocytic Ca2+ elevations are closely associated with diameter changes in the nearby blood vessels, which astrocytes enwrap with their endfeet. However, the causal relationship between astrocytic Ca2+ elevations and blood vessel diameter changes has been questioned, as mice with diminished astrocytic Ca2+ signaling show normal sensory hyperemia. We addressed this controversy by imaging cortical vasculature while optogenetically elevating astrocyte Ca2+ in a novel transgenic mouse line, expressing Opto-Gq-type GPCR Optoα1AR (Astro-Optoα1AR) in astrocytes. Blue light illumination on the surface of the somatosensory cortex induced Ca2+ elevations in cortical astrocytes and their endfeet in mice under anesthesia. Blood vessel diameter did not change significantly with Optoα1AR-induced Ca2+ 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-Optoα1AR 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 Ca2+ signaling.",
keywords = "astrocytes, blood flow, Ca elevation, cortex, mouse, optical imaging, OptoA1AR, optogenetic GPCR",
author = "Katsuya Ozawa and Masaki Nagao and Ayumu Konno and Youichi Iwai and Marta Vittani and Peter Kusk and Tsuneko Mishima and Hirokazu Hirai and Maiken Nedergaard and Hajime Hirase",
note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
doi = "10.3390/ijms241713590",
language = "English",
volume = "24",
journal = "International Journal of Molecular Sciences (Online)",
issn = "1661-6596",
publisher = "MDPI AG",
number = "17",

}

RIS

TY - JOUR

T1 - Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes

AU - Ozawa, Katsuya

AU - Nagao, Masaki

AU - Konno, Ayumu

AU - Iwai, Youichi

AU - Vittani, Marta

AU - Kusk, Peter

AU - Mishima, Tsuneko

AU - Hirai, Hirokazu

AU - Nedergaard, Maiken

AU - Hirase, Hajime

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - Activation of Gq-type G protein-coupled receptors (GPCRs) gives rise to large cytosolic Ca2+ elevations in astrocytes. Previous in vitro and in vivo studies have indicated that astrocytic Ca2+ elevations are closely associated with diameter changes in the nearby blood vessels, which astrocytes enwrap with their endfeet. However, the causal relationship between astrocytic Ca2+ elevations and blood vessel diameter changes has been questioned, as mice with diminished astrocytic Ca2+ signaling show normal sensory hyperemia. We addressed this controversy by imaging cortical vasculature while optogenetically elevating astrocyte Ca2+ in a novel transgenic mouse line, expressing Opto-Gq-type GPCR Optoα1AR (Astro-Optoα1AR) in astrocytes. Blue light illumination on the surface of the somatosensory cortex induced Ca2+ elevations in cortical astrocytes and their endfeet in mice under anesthesia. Blood vessel diameter did not change significantly with Optoα1AR-induced Ca2+ 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-Optoα1AR 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 Ca2+ signaling.

AB - Activation of Gq-type G protein-coupled receptors (GPCRs) gives rise to large cytosolic Ca2+ elevations in astrocytes. Previous in vitro and in vivo studies have indicated that astrocytic Ca2+ elevations are closely associated with diameter changes in the nearby blood vessels, which astrocytes enwrap with their endfeet. However, the causal relationship between astrocytic Ca2+ elevations and blood vessel diameter changes has been questioned, as mice with diminished astrocytic Ca2+ signaling show normal sensory hyperemia. We addressed this controversy by imaging cortical vasculature while optogenetically elevating astrocyte Ca2+ in a novel transgenic mouse line, expressing Opto-Gq-type GPCR Optoα1AR (Astro-Optoα1AR) in astrocytes. Blue light illumination on the surface of the somatosensory cortex induced Ca2+ elevations in cortical astrocytes and their endfeet in mice under anesthesia. Blood vessel diameter did not change significantly with Optoα1AR-induced Ca2+ 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-Optoα1AR 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 Ca2+ signaling.

KW - astrocytes

KW - blood flow

KW - Ca elevation

KW - cortex

KW - mouse

KW - optical imaging

KW - OptoA1AR

KW - optogenetic GPCR

U2 - 10.3390/ijms241713590

DO - 10.3390/ijms241713590

M3 - Journal article

C2 - 37686396

AN - SCOPUS:85170379908

VL - 24

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 17

M1 - 13590

ER -

ID: 371280675