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
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
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
Article's DOI: 10.1113/JP278640
Entity: Universitat Rovira i Virgili
Journal publication year: 2019
Publication Type: Journal Publications
Repositori URV