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Cited by 147Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Modulation of the autonomic nervous system and behaviour by acute glial cell G q protein‐coupled receptor activation in vivo

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Agulhon, Cendra, Boyt, Kristen M., Xie, Alison Xiaoqiao, Friocourt, Francois, Roth, Bryan L., McCarthy, Ken D.·2013·The Journal of Physiology
DOI 10.1113/jphysiol.2013.261289PMC PMC3853498
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Abstract

Key points: The activation of glial G q protein‐coupled receptor (G q ‐GPCR) signalling cascades broadly activates the autonomic nervous system The activation of glial G q ‐GPCR signalling cascades affects activity‐related behaviour. Abstract: Glial fibrillary acidic protein (GFAP)‐expressing cells (GFAP + glial cells) are the predominant cell type in the central and peripheral nervous systems. Our understanding of the role of GFAP + glial cells and their signalling systems in vivo is limited due to our inability to manipulate these cells and their receptors in a cell type‐specific and non‐invasive manner. To circumvent this limitation, we developed a transgenic mouse line (GFAP‐hM3Dq mice) that expresses an engineered G q protein‐coupled receptor (G q ‐GPCR) known as hM3Dq DREADD (designer receptor exclusively activated by designer drug) selectively in GFAP + glial cells. The hM3Dq receptor is activated solely by a pharmacologically inert, but bioavailable, ligand (clozapine‐ N ‐oxide; CNO), while being non‐responsive to endogenous GPCR ligands. In GFAP‐hM3Dq mice, CNO administration increased heart rate, blood pressure and saliva formation, as well as decreased body temperature, parameters that are controlled by the autonomic nervous system (ANS). Additionally, changes in activity‐related behaviour and motor coordination were observed following CNO administration. Genetically blocking inositol 1,4,5‐trisphosphate (IP 3 )‐dependent Ca 2+ increases in astrocytes failed to interfere with CNO‐mediated changes in ANS function, locomotor activity or motor coordination. Our findings reveal an unexpectedly broad role of GFAP + glial cells in modulating complex physiology and behaviour in vivo and suggest that these effects are not dependent on IP 3 ‐dependent increases in astrocytic Ca 2+ .

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  • Previous studies have expressed the Gq-DREADD specifically in astrocytes using the GFAP promotor and showed an increase in intracellular Ca2+ after activation with CNO.

    “Previous studies have expressed the Gq-DREADD specifically in astrocytes using the GFAP promotor and showed an increase in intracellular Ca 2+ after activation with CNO (Agulhon et al., 2013;Bull et al., 2014;Scofield et al., 2015).”

    From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Agulhon et al., 2013

    The Discussion says hM3Dq DREADD was expressed under the GFAP promoter and restricted to astrocytes within the CNS, but also expressed in non-myelinating Schwann cells and satellite cells in the PNS. The Results report CNO-induced Ca2+ increases in 95.51% of hippocampal astrocytes. Thus the activation finding is supported, but expression was not specific to astrocytes throughout the mouse. (LLM, conf=0.88)

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  • This is the first study to show transcriptional changes in glia that occur after long-term activation of astrocytes with the Gq-DREADD in an in vivo model.

    “To the best of our knowledge, this is the first study to show transcriptional changes in glia that occur after long-term activation of astrocytes with the Gq-DREADD in an in vivo model.”

    From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Agulhon et al., 2013

  • None of these previous studies looked at the effect of long-term Gq-DREADD-mediated activation on the transcriptome of astrocytes or other neighboring brain cells.

    “However, none of these studies looked at the effect of long-term Gq-DREADD-mediated activation on the transcriptome of astrocytes or other neighboring brain cells.”

    From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Agulhon et al., 2013

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Sorted by citations

Authors
Agulhon, C., Boyt, K. M., Xie, A. X., Friocourt, F., Roth, B. L., & McCarthy, K. D.
Affiliations
University of North Carolina at Chapel Hill (US)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2013-10-23
Volume
591
Issue
22
Pages
5599-5609
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2013.261289
PMC
PMC3853498
OpenAlex
W1563267988
Cited by
147
References
4
Citations by year
2026: 3 · 2025: 8 · 2024: 9 · 2023: 10 · 2022: 7 · 2021: 15 · 2020: 18 · 2019: 19 · 2018: 14 · 2017: 11 · 2016: 13 · 2015: 12 · 2014: 7 · 2013: 1
FWCI
5.40
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (U19MH082441, U19-MH82441)
  • National Institute of Neurological Disorders and Stroke (R01-NS020212-26, R01NS020212)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (#HD03110, P30HD003110)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
glial cells, glial fibrillary acidic protein, Gq protein-coupled receptors, clozapine-N-oxide, autonomic nervous system, heart rate, blood pressure, salivary secretion, body temperature, locomotor activity, motor coordination, astrocytes, transgenic mice
MeSH terms
Animals, Astrocytes, Autonomic Nervous System, Calcium, Glial Fibrillary Acidic Protein, Ligands, Mice, Transgenic, Motor Activity, Neuroglia, Neurons, Signal Transduction, Inositol 1,4,5-Trisphosphate, Mice, Knockout, Receptors, G-Protein-Coupled, Mice

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