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Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice

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Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice. / Wenzel, Jan; Hansen, Cathrin E; Bettoni, Carla; Vogt, Miriam A; Lembrich, Beate; Natsagdorj, Rentsenkhand; Huber, Gianna; Brands, Josefine; Schmidt, Kjestine; Assmann, Julian C; Stölting, Ines; Saar, Kathrin; Sedlacik, Jan; Fiehler, Jens; Ludewig, Peter; Wegmann, Michael; Feller, Nina; Richter, Marius; Müller-Fielitz, Helge; Walther, Thomas; König, Gabriele M; Kostenis, Evi; Raasch, Walter; Hübner, Norbert; Gass, Peter; Offermanns, Stefan; de Wit, Cor; Wagner, Carsten A; Schwaninger, Markus.

in: P NATL ACAD SCI USA, Jahrgang 117, Nr. 3, 21.01.2020, S. 1753-1761.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wenzel, J, Hansen, CE, Bettoni, C, Vogt, MA, Lembrich, B, Natsagdorj, R, Huber, G, Brands, J, Schmidt, K, Assmann, JC, Stölting, I, Saar, K, Sedlacik, J, Fiehler, J, Ludewig, P, Wegmann, M, Feller, N, Richter, M, Müller-Fielitz, H, Walther, T, König, GM, Kostenis, E, Raasch, W, Hübner, N, Gass, P, Offermanns, S, de Wit, C, Wagner, CA & Schwaninger, M 2020, 'Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice', P NATL ACAD SCI USA, Jg. 117, Nr. 3, S. 1753-1761. https://doi.org/10.1073/pnas.1907467117, https://doi.org/10.1073/pnas.1907467117

APA

Wenzel, J., Hansen, C. E., Bettoni, C., Vogt, M. A., Lembrich, B., Natsagdorj, R., Huber, G., Brands, J., Schmidt, K., Assmann, J. C., Stölting, I., Saar, K., Sedlacik, J., Fiehler, J., Ludewig, P., Wegmann, M., Feller, N., Richter, M., Müller-Fielitz, H., ... Schwaninger, M. (2020). Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice. P NATL ACAD SCI USA, 117(3), 1753-1761. https://doi.org/10.1073/pnas.1907467117, https://doi.org/10.1073/pnas.1907467117

Vancouver

Wenzel J, Hansen CE, Bettoni C, Vogt MA, Lembrich B, Natsagdorj R et al. Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice. P NATL ACAD SCI USA. 2020 Jan 21;117(3):1753-1761. https://doi.org/10.1073/pnas.1907467117, https://doi.org/10.1073/pnas.1907467117

Bibtex

@article{be4f7496419943a98d7ed395a87a6d51,
title = "Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice",
abstract = "Carbon dioxide (CO2), the major product of metabolism, has a strong impact on cerebral blood vessels, a phenomenon known as cerebrovascular reactivity. Several vascular risk factors such as hypertension or diabetes dampen this response, making cerebrovascular reactivity a useful diagnostic marker for incipient vascular pathology, but its functional relevance, if any, is still unclear. Here, we found that GPR4, an endothelial H+ receptor, and endothelial Gαq/11 proteins mediate the CO2/H+ effect on cerebrovascular reactivity in mice. CO2/H+ leads to constriction of vessels in the brainstem area that controls respiration. The consequential washout of CO2, if cerebrovascular reactivity is impaired, reduces respiration. In contrast, CO2 dilates vessels in other brain areas such as the amygdala. Hence, an impaired cerebrovascular reactivity amplifies the CO2 effect on anxiety. Even at atmospheric CO2 concentrations, impaired cerebrovascular reactivity caused longer apneic episodes and more anxiety, indicating that cerebrovascular reactivity is essential for normal brain function. The site-specific reactivity of vessels to CO2 is reflected by regional differences in their gene expression and the release of vasoactive factors from endothelial cells. Our data suggest the central nervous system (CNS) endothelium as a target to treat respiratory and affective disorders associated with vascular diseases.",
keywords = "Amygdala, Animals, Anxiety/metabolism, Arterioles/pathology, Brain/physiology, Brain Stem/metabolism, Carbon Dioxide/metabolism, Cardiovascular System/metabolism, Central Nervous System/metabolism, Disease Models, Animal, Endothelium/metabolism, GTP-Binding Protein alpha Subunits, Gq-G11/genetics, Gene Expression, Humans, Hypercapnia/metabolism, Mice, Mice, Knockout, Mice, Transgenic, Receptors, G-Protein-Coupled/genetics, Respiration, Respiration Disorders/metabolism, Risk Factors, Signal Transduction",
author = "Jan Wenzel and Hansen, {Cathrin E} and Carla Bettoni and Vogt, {Miriam A} and Beate Lembrich and Rentsenkhand Natsagdorj and Gianna Huber and Josefine Brands and Kjestine Schmidt and Assmann, {Julian C} and Ines St{\"o}lting and Kathrin Saar and Jan Sedlacik and Jens Fiehler and Peter Ludewig and Michael Wegmann and Nina Feller and Marius Richter and Helge M{\"u}ller-Fielitz and Thomas Walther and K{\"o}nig, {Gabriele M} and Evi Kostenis and Walter Raasch and Norbert H{\"u}bner and Peter Gass and Stefan Offermanns and {de Wit}, Cor and Wagner, {Carsten A} and Markus Schwaninger",
year = "2020",
month = jan,
day = "21",
doi = "https://doi.org/10.1073/pnas.1907467117",
language = "English",
volume = "117",
pages = "1753--1761",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "3",

}

RIS

TY - JOUR

T1 - Impaired Endothelium-Mediated Cerebrovascular Reactivity Promotes Anxiety and Respiration Disorders in Mice

AU - Wenzel, Jan

AU - Hansen, Cathrin E

AU - Bettoni, Carla

AU - Vogt, Miriam A

AU - Lembrich, Beate

AU - Natsagdorj, Rentsenkhand

AU - Huber, Gianna

AU - Brands, Josefine

AU - Schmidt, Kjestine

AU - Assmann, Julian C

AU - Stölting, Ines

AU - Saar, Kathrin

AU - Sedlacik, Jan

AU - Fiehler, Jens

AU - Ludewig, Peter

AU - Wegmann, Michael

AU - Feller, Nina

AU - Richter, Marius

AU - Müller-Fielitz, Helge

AU - Walther, Thomas

AU - König, Gabriele M

AU - Kostenis, Evi

AU - Raasch, Walter

AU - Hübner, Norbert

AU - Gass, Peter

AU - Offermanns, Stefan

AU - de Wit, Cor

AU - Wagner, Carsten A

AU - Schwaninger, Markus

PY - 2020/1/21

Y1 - 2020/1/21

N2 - Carbon dioxide (CO2), the major product of metabolism, has a strong impact on cerebral blood vessels, a phenomenon known as cerebrovascular reactivity. Several vascular risk factors such as hypertension or diabetes dampen this response, making cerebrovascular reactivity a useful diagnostic marker for incipient vascular pathology, but its functional relevance, if any, is still unclear. Here, we found that GPR4, an endothelial H+ receptor, and endothelial Gαq/11 proteins mediate the CO2/H+ effect on cerebrovascular reactivity in mice. CO2/H+ leads to constriction of vessels in the brainstem area that controls respiration. The consequential washout of CO2, if cerebrovascular reactivity is impaired, reduces respiration. In contrast, CO2 dilates vessels in other brain areas such as the amygdala. Hence, an impaired cerebrovascular reactivity amplifies the CO2 effect on anxiety. Even at atmospheric CO2 concentrations, impaired cerebrovascular reactivity caused longer apneic episodes and more anxiety, indicating that cerebrovascular reactivity is essential for normal brain function. The site-specific reactivity of vessels to CO2 is reflected by regional differences in their gene expression and the release of vasoactive factors from endothelial cells. Our data suggest the central nervous system (CNS) endothelium as a target to treat respiratory and affective disorders associated with vascular diseases.

AB - Carbon dioxide (CO2), the major product of metabolism, has a strong impact on cerebral blood vessels, a phenomenon known as cerebrovascular reactivity. Several vascular risk factors such as hypertension or diabetes dampen this response, making cerebrovascular reactivity a useful diagnostic marker for incipient vascular pathology, but its functional relevance, if any, is still unclear. Here, we found that GPR4, an endothelial H+ receptor, and endothelial Gαq/11 proteins mediate the CO2/H+ effect on cerebrovascular reactivity in mice. CO2/H+ leads to constriction of vessels in the brainstem area that controls respiration. The consequential washout of CO2, if cerebrovascular reactivity is impaired, reduces respiration. In contrast, CO2 dilates vessels in other brain areas such as the amygdala. Hence, an impaired cerebrovascular reactivity amplifies the CO2 effect on anxiety. Even at atmospheric CO2 concentrations, impaired cerebrovascular reactivity caused longer apneic episodes and more anxiety, indicating that cerebrovascular reactivity is essential for normal brain function. The site-specific reactivity of vessels to CO2 is reflected by regional differences in their gene expression and the release of vasoactive factors from endothelial cells. Our data suggest the central nervous system (CNS) endothelium as a target to treat respiratory and affective disorders associated with vascular diseases.

KW - Amygdala

KW - Animals

KW - Anxiety/metabolism

KW - Arterioles/pathology

KW - Brain/physiology

KW - Brain Stem/metabolism

KW - Carbon Dioxide/metabolism

KW - Cardiovascular System/metabolism

KW - Central Nervous System/metabolism

KW - Disease Models, Animal

KW - Endothelium/metabolism

KW - GTP-Binding Protein alpha Subunits, Gq-G11/genetics

KW - Gene Expression

KW - Humans

KW - Hypercapnia/metabolism

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Receptors, G-Protein-Coupled/genetics

KW - Respiration

KW - Respiration Disorders/metabolism

KW - Risk Factors

KW - Signal Transduction

U2 - https://doi.org/10.1073/pnas.1907467117

DO - https://doi.org/10.1073/pnas.1907467117

M3 - SCORING: Journal article

C2 - 31896584

VL - 117

SP - 1753

EP - 1761

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 3

ER -