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Psychoneuroimmunology pp 341–352Cite as

Sculpting the Sculptors: Methods for Studying the Fetal Cholinergic Signaling on Systems and Cellular Scales

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1781))

Abstract

The non-neuronal, immunological effects of the cholinergic signaling are exerted on the system’s scale of observation via the vagus nerve and on the cellular scale via α7 nicotinic acetylcholine receptor (nAChR) signaling in myeloid cells of the periphery or brain’s microglia and astrocytes. The developmental effects of such multi-scale signaling can be conceived of as an example of psychoneuroimmunological (PNI) homeokinesis and, while reported in the literature, are not yet systematically well studied. To be better understood, the intricacy of the multi-scale interactions requires relevant preclinical animal models. Chronically instrumented non-anesthetized fetal sheep model comes with a strong track record of bench-to-bed translation and a large body of evidence for its strong resemblance to and relevance for human physiology on various scales of organization. Recently, there has been growing interest in pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity, metabolism, and emotion with implications for programming of PNI phenotype. Here we describe the procedures required to record and manipulate the vagus nerve activity in this large pregnant mammalian organism. Extending this in vivo model to in vitro, on the cellular scale, we present the method to manipulate the cholinergic signaling in ovine fetal microglia and astrocytes and analyze their responses on protein and RNA levels. Together these models can provide multi-scale-level mechanistic insights into the effects of cholinergic signaling on PNI phenotype.

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Acknowledgments

The authors gratefully acknowledge funding support from the Molly Towell Perinatal Research Foundation, Canadian Institutes of Health Research (CIHR), and Fonds de Recherche du Québec—Santé (FRQS) (to MGF).

The authors wish to thank Esther Simard, Marco Bosa, Carl Bernard, Dr. Lucien Daniel Durosier, Hai Lun Liu, and Carmen Movila for technical assistance and Jan Hamanishi for graphical design.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Washington, Seattle, WA, USA

    Martin G. Frasch

  2. Department of Obstetrics and Gynaecology, CHU Ste-Justine Research Centre, University of Montreal, Montreal, QC, Canada

    Martin G. Frasch & Mingju Cao

  3. Department of Neurosciences, CHU Ste-Justine Research Centre, University of Montreal, Montreal, QC, Canada

    Martin G. Frasch & Mingju Cao

  4. Centre de Recherche en Reproduction Animale (CRRA), University of Montreal, St-Hyacinthe, QC, Canada

    Martin G. Frasch & Marina Cortes

  5. Bristol Veterinary School, University of Bristol, Bristol, UK

    Patrick Burns

  6. Faculty of Veterinary Medicine, Department of Clinical Sciences, University of Montreal, St-Hyacinthe, QC, Canada

    Javier Benito, Gilles Fecteau & André Desrochers

Authors
  1. Martin G. Frasch
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  2. Patrick Burns
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  3. Javier Benito
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  4. Marina Cortes
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  5. Mingju Cao
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  6. Gilles Fecteau
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  7. André Desrochers
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Corresponding author

Correspondence to Martin G. Frasch .

Editor information

Editors and Affiliations

  1. University of Maryland University College, Adelphi, MD, PharmTao, Santa Clara, California, USA

    Qing Yan

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Frasch, M.G. et al. (2018). Sculpting the Sculptors: Methods for Studying the Fetal Cholinergic Signaling on Systems and Cellular Scales. In: Yan, Q. (eds) Psychoneuroimmunology. Methods in Molecular Biology, vol 1781. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7828-1_18

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  • DOI: https://doi.org/10.1007/978-1-4939-7828-1_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7827-4

  • Online ISBN: 978-1-4939-7828-1

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