skip to main content


Title: Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis: ROLE OF SEROTONIN AND CATECHOLAMINES IN GUT/BRAIN AXIS
NSF-PAR ID:
10036842
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Journal of Cellular Physiology
Volume:
232
Issue:
9
ISSN:
0021-9541
Page Range / eLocation ID:
2359 to 2372
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Bacterial extracellular vesicles (BEVs) have emerged as candidate signaling vectors for long‐distance interkingdom communication within the gut‐microbiota brain axis. Most bacteria release these nanosized vesicles, capable of signaling to the brain via their abundant protein and small RNA cargo, possibly directly via crossing the blood‐brain barrier. BEVs have been shown to regulate brain gene expression and induce pathology at most stages of neuroinflammation and neurodegeneration, and thus they may play a causal role in diseases such as Alzheimer's, Parkinson's, and depression/anxiety. On the other hand, BEVs have intrinsic therapeutic properties that may be relevant to probiotic therapy and can also be engineered to function as drug delivery vehicles and vaccines. Thus, BEVs may be both a cause of and solution to neuropathological conditions. In this review, current knowledge of the physiological roles of BEVs as well as state of the art pertaining to the development of therapeutic BEVs in the context of the microbiome‐gut‐brain axis are summarized.

     
    more » « less
  2. 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.

     
    more » « less
  3. Abstract

    Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.

     
    more » « less