Nod-like receptors are critical for gut-brain axis signalling in mice
| Autor: | Ciara E. Keogh, Matteo M. Pusceddu, Mariana Barboza, Dana J. Philpott, Colin Reardon, Charles Maisonneuve, Carlito B. Lebrilla, Kim E. Barrett, Gonzalo Rabasa, Ingrid Brust-Mascher, Richard L. Ferrero, Lily R. Goldfild, Mélanie G. Gareau, Mariana X. Byndloss, Melinda Schneider, Kyle Akio Wong, Andreas J. Bäumler, Shane E. Gillis, HyunJung Kim, Jessica A. Sladek, Cristina Torres-Fuentes, Patricia Stokes |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male cognition Physiology Nod2 Signaling Adaptor Protein Nod Anxiety Inbred C57BL Synaptic Transmission Medical and Health Sciences Oral and gastrointestinal Mice Cognition 0302 clinical medicine Nod1 Signaling Adaptor Protein 2.1 Biological and endogenous factors Intestinal Mucosa Aetiology Receptor microbiota-gut-brain axis Cells Cultured Cultured Depression Pattern recognition receptor Brain intestinal physiology Biological Sciences Cell biology Mental Health Female 5-HT system Hypothalamo-Hypophyseal System Serotonin Serotonin reuptake inhibitor Cells Neurogenesis 1.1 Normal biological development and functioning Gut–brain axis Biology Serotonergic Stress NLR 03 medical and health sciences Underpinning research Behavioral and Social Science Animals Innate immune system HPA axis Neurosciences Mice Inbred C57BL 030104 developmental biology Intestinal Absorption Psychological Digestive Diseases Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | The Journal of physiology, vol 597, iss 24 |
| Popis: | Key points •Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like receptors regulate central and peripheral serotonergic biology. •Nod-like receptors are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression of Nod1 receptors regulate behaviour. Abstract Gut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+ Nod1f/f ), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders. |
| Databáze: | OpenAIRE |
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