Articles producció científica> Bioquímica i Biotecnologia

Nod-like receptors are critical for gut-brain axis signalling in mice

  • Identification data

    Identifier: imarina:6010705
    Authors:
    Pusceddu, MMBarboza, MKeogh, CESchneider, MStokes, PSladek, JAKim, HJDTorres-Fuentes, CGoldfild, LRGillis, SEBrust-Mascher, IRabasa, GWong, KALebrilla, CByndloss, MXMaisonneuve, CBäumler, AJPhilpott, DJFerrero, RLBarrett, KEReardon, CGareau, MG
    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(+)Nod1(f/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.
  • Others:

    Author, as appears in the article.: Pusceddu, MM; Barboza, M; Keogh, CE; Schneider, M; Stokes, P; Sladek, JA; Kim, HJD; Torres-Fuentes, C; Goldfild, LR; Gillis, SE; Brust-Mascher, I; Rabasa, G; Wong, KA; Lebrilla, C; Byndloss, MX; Maisonneuve, C; Bäumler, AJ; Philpott, DJ; Ferrero, RL; Barrett, KE; Reardon, C; Gareau, MG
    Department: Bioquímica i Biotecnologia
    URV's Author/s: Torres Fuentes, Cristina
    Keywords: Synaptic plasticity Stress Serotonin Recognition Rat Psychological stress Nlr Neurogenesis Mineralocorticoid receptor Microbiota-gut–brain axis Microbiota-gut-brain axis Microbiota Intestinal physiology Hpa axis Fluoxetine Expression Depression Cognition Anxiety Adult hippocampal neurogenesis 5-ht system nlr neurogenesis microbiota-gut-brain axis intestinal physiology hpa axis depression cognition anxiety 5-ht system
    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(+)Nod1(f/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.
    Thematic Areas: Sports science Química Psicología Physiology Odontología Nutrição Neurosciences Medicina iii Medicina ii Medicina i Interdisciplinar Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biodiversidade
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 00223751
    Author's mail: cristina.torres@urv.cat
    Author identifier: 0000-0002-2917-6910
    Record's date: 2024-02-11
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP278640
    Papper original source: Journal Of Physiology-London. 597 (24): 5777-5797
    APA: Pusceddu, MM; Barboza, M; Keogh, CE; Schneider, M; Stokes, P; Sladek, JA; Kim, HJD; Torres-Fuentes, C; Goldfild, LR; Gillis, SE; Brust-Mascher, I; Rab (2019). Nod-like receptors are critical for gut-brain axis signalling in mice. Journal Of Physiology-London, 597(24), 5777-5797. DOI: 10.1113/JP278640
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1113/JP278640
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2019
    Publication Type: Journal Publications
  • Keywords:

    Neurosciences,Physiology,Sports Science
    Synaptic plasticity
    Stress
    Serotonin
    Recognition
    Rat
    Psychological stress
    Nlr
    Neurogenesis
    Mineralocorticoid receptor
    Microbiota-gut–brain axis
    Microbiota-gut-brain axis
    Microbiota
    Intestinal physiology
    Hpa axis
    Fluoxetine
    Expression
    Depression
    Cognition
    Anxiety
    Adult hippocampal neurogenesis
    5-ht system
    nlr
    neurogenesis
    microbiota-gut-brain axis
    intestinal physiology
    hpa axis
    depression
    cognition
    anxiety
    5-ht system
    Sports science
    Química
    Psicología
    Physiology
    Odontología
    Nutrição
    Neurosciences
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Farmacia
    Engenharias iv
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biodiversidade
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