Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice

Lansbury, Elizabeth Laura; Vana, Vasiliki; Lund, Mari Lilith; Ludwig, Mette Q.; Mamedova, Esmira; Gautron, Laurent; Arnold, Myrtha; Egerod, Kristoffer Lihme; Kuhre, Rune Ehrenreich; Holst, Jens Juul; Rekling, Jens; Schwartz, Thue W.; Pankratova, Stanislava; Dmytriyeva, Oksana

doi:10.3390/ijms26052053

Open AccessArticle

Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice

by

Elizabeth Laura Lansbury

^1,†

,

Vasiliki Vana

^1,†,

Mari Lilith Lund

¹

,

Mette Q. Ludwig

¹,

Esmira Mamedova

²,

Laurent Gautron

³

,

Myrtha Arnold

⁴,

Kristoffer Lihme Egerod

¹

,

Rune Ehrenreich Kuhre

^1,5,

Jens Juul Holst

^1,5

,

Jens Rekling

²

,

Thue W. Schwartz

¹,

Stanislava Pankratova

^1,6

and

Oksana Dmytriyeva

^1,*

¹

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark

²

Institute of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

³

Center for Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

⁴

Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland

⁵

Department for Biomedical Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

⁶

Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Copenhagen, Denmark

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(5), 2053; https://doi.org/10.3390/ijms26052053

Submission received: 9 January 2025 / Revised: 24 February 2025 / Accepted: 24 February 2025 / Published: 26 February 2025

(This article belongs to the Section Molecular Endocrinology and Metabolism)

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Abstract

Afferent vagal neurons convey gut–brain signals related to the mechanical and chemical sensing of nutrients, with the latter also mediated by gut hormones secreted from enteroendocrine cells. Cell bodies of these neurons are located in the nodose ganglia (NG), with the right NG playing a key role in metabolic regulation. Notably, glucagon-like peptide-1 receptor (GLP1R) neurons primarily innervate the muscle layer of the stomach, distant from glucagon-like peptide-1 (GLP-1)-secreting gut cells. However, the co-expression of gut hormone receptors in these NG neurons remains unclear. Using RNAscope combined with immunohistochemistry, we confirmed GLP1R expression in a large population of NG neurons, with Glp1r, cholecystokinin A receptor (Cckar), and Neuropeptide Y Y2 Receptor (Npy2r) being more highly expressed in the right NG, while neurotensin receptor 1 (Ntsr), G protein-coupled receptor (Gpr65), and 5-hydroxytryptamine receptor 3A (5ht3a) showed equal expressions in the left and right NG. Co-expression analysis demonstrated the following: (i) most Glp1r, Cckar, and Npy2r neurons co-expressed all three receptors; (ii) nearly all Ntsr1- and Gpr65-positive neurons co-expressed both receptors; and (iii) 5ht3a was expressed in subpopulations of all peptide-hormone-receptor-positive neurons. Retrograde labeling demonstrated that the anterior part of the stomach was preferentially innervated by the left NG, while the right NG innervated the posterior part. The entire gastrointestinal (GI) tract, including the distal colon, was strongly innervated by NG neurons. Most importantly, dual retrograde labeling with two distinct tracers identified a population of neurons co-expressing Glp1r, Cckar, and Npy2r that innervated both the stomach and the colon. Thus, neurons co-expressing GLP-1, cholecystokinin (CCK), and peptide YY (PYY) receptors, predominantly found in the right NG, sample chemical, nutrient-induced signals along the entire GI tract and likely integrate these with mechanical signals from the stomach.

Keywords: nodose ganglia; vagal afferent neurons; GLP-1 receptor; CCKa receptor; NPY2 receptor; neurotensin receptor

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MDPI and ACS Style

Lansbury, E.L.; Vana, V.; Lund, M.L.; Ludwig, M.Q.; Mamedova, E.; Gautron, L.; Arnold, M.; Egerod, K.L.; Kuhre, R.E.; Holst, J.J.; et al. Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice. Int. J. Mol. Sci. 2025, 26, 2053. https://doi.org/10.3390/ijms26052053

AMA Style

Lansbury EL, Vana V, Lund ML, Ludwig MQ, Mamedova E, Gautron L, Arnold M, Egerod KL, Kuhre RE, Holst JJ, et al. Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice. International Journal of Molecular Sciences. 2025; 26(5):2053. https://doi.org/10.3390/ijms26052053

Chicago/Turabian Style

Lansbury, Elizabeth Laura, Vasiliki Vana, Mari Lilith Lund, Mette Q. Ludwig, Esmira Mamedova, Laurent Gautron, Myrtha Arnold, Kristoffer Lihme Egerod, Rune Ehrenreich Kuhre, Jens Juul Holst, and et al. 2025. "Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice" International Journal of Molecular Sciences 26, no. 5: 2053. https://doi.org/10.3390/ijms26052053

APA Style

Lansbury, E. L., Vana, V., Lund, M. L., Ludwig, M. Q., Mamedova, E., Gautron, L., Arnold, M., Egerod, K. L., Kuhre, R. E., Holst, J. J., Rekling, J., Schwartz, T. W., Pankratova, S., & Dmytriyeva, O. (2025). Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice. International Journal of Molecular Sciences, 26(5), 2053. https://doi.org/10.3390/ijms26052053

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Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice

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