The aryl hydrocarbon receptor and the gut–brain axis

Barroso, Andréia; Mahler, João Vitor; Fonseca-Castro, Pedro Henrique; Quintana, Francisco J.

doi:10.1038/s41423-020-00585-5

Cited by 79 publications

(52 citation statements)

References 155 publications

(200 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ligand-bound AhR translocates from the cytoplasm into the nucleus and enhances the expression of AhR-target genes, such as Cyp1a1 and Cyp1b1 , whereas these are not activated in Ahr −/− mice (Mimura and Fujii-Kuriyama 2003 ). To date, evidence has accumulated to indicate the presence of endogenous and exogenous substances that act as AhR ligands (Barroso et al 2021 ). An intake of indole-3-carbinol, a dietary AhR ligand, induces expression of Cyp1a1 mRNA in the small intestine of the mouse (Li et al 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain

Kimura

Kohda

Maekawa

et al. 2021

Histochem Cell Biol

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AhR) acts as a receptor that responds to ligands, including dioxin. The AhR–ligand complex translocates from the cytoplasm into the nucleus to induce gene expression. Because dioxin exposure impairs cognitive and neurobehavioral functions, AhR-expressing neurons need to be identified for elucidation of the dioxin neurotoxicity mechanism. Immunohistochemistry was performed to detect AhR-expressing neurons in the mouse brain and confirm the specificity of the anti-AhR antibody using Ahr−/− mice. Intracellular distribution of AhR and expression level of AhR-target genes, Cyp1a1, Cyp1b1, and Ahr repressor (Ahrr), were analyzed by immunohistochemistry and quantitative RT-PCR, respectively, using mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mouse brains were shown to harbor AhR in neurons of the locus coeruleus (LC) and island of Calleja major (ICjM) during developmental period in Ahr+/+ mice but not in Ahr−/− mice. A significant increase in nuclear AhR of ICjM neurons but not LC neurons was found in 14-day-old mice compared to 5- and 7-day-old mice. AhR was significantly translocated into the nucleus in LC and ICjM neurons of TCDD-exposed adult mice. Additionally, the expression levels of Cyp1a1, Cyp1b1, and Ahrr genes in the brain, a surrogate of TCDD in the tissue, were significantly increased by dioxin exposure, suggesting that dioxin-activated AhR induces gene expression in LC and ICjM neurons. This histochemical study shows the ligand-induced nuclear translocation of AhR at the single-neuron level in vivo. Thus, the neurotoxicological significance of the dioxin-activated AhR in the LC and ICjM warrants further studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain

Kimura

Kohda

Maekawa

et al. 2021

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…Native T cells that are involved in immune surveillance also express AhR, which, when activated by kynurenine, aids in the resolution of inflammation in several tissues by driving the differentiation of Tregs that secrete anti-inflammatory cytokines [117,118]. Dietary indoles, such indole-3-carbinol, and gut microbiota-derived indoles, such as indoxyl-3-sulfate, activate glial cells through AhR to mediate the response to CNS inflammation (Figure 3) [119,120]. These metabolites activate AhR, which in turn inhibits NF-κB by increasing the expression of SOCS2 protein (a suppressor of cytokine signaling) in astrocyte cells [121].…”

Section: Inflammation and Glial Cell Activationmentioning

confidence: 99%

The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe

Ojo

Tischkau

2021

Cells

View full text Add to dashboard Cite

In recent years, aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered to be involved in aging phenotypes across several species. This receptor is a highly conserved biosensor that is activated by numerous exogenous and endogenous molecules, including microbiota metabolites, to mediate several physiological and toxicological functions. Brain aging hallmarks, which include glial cell activation and inflammation, increased oxidative stress, mitochondrial dysfunction, and cellular senescence, increase the vulnerability of humans to various neurodegenerative diseases. Interestingly, many studies have implicated AhR signaling pathways in the aging process and longevity across several species. This review provides an overview of the impact of AhR pathways on various aging hallmarks in the brain and the implications for AhR signaling as a mechanism in regulating aging-related diseases of the brain. We also explore how the nature of AhR ligands determines the outcomes of several signaling pathways in brain aging processes.

show abstract

“…In recent years, the number of publications on the role of the aryl hydrocarbon receptor (AhR) in the regulation of the functions of the nervous system cells has increased (Juricek and Coumoul 2018;Barroso et al 2021). AhR integrates environmental, dietary, microbial, and metabolic signals to control transcriptional programs in a ligand-specific, cell type-specific, and context-specific manner (Rothhammer and Quintana 2019).…”

Section: Nuclear Receptors Pparγ and Ahrmentioning

confidence: 99%

Elastin-Derived Peptides in the Central Nervous System: Friend or Foe

2021

View full text Add to dashboard Cite

Elastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display incredible resilience and structural stability with long half-life. However, during some physiological and pathophysiological conditions, elastin is prone to proteolytic degradation and, due to the extremely low turnover rate, its degradation is practically an irreversible and irreparable phenomenon. As a result of elastin degradation, new peptides called elastin-derived peptides (EDPs) are formed. A growing body of evidence suggests that these peptides play an important role in the development of age-related vascular disease. They are also detected in the cerebrospinal fluid of healthy people, and their amount increases in patients after ischemic stroke. Recently, elastin-like polypeptides have been reported to induce overproduction of beta-amyloid in a model of Alzheimer's disease. Nevertheless, the role and mechanism of action of EDPs in the nervous system is largely unknown and limited to only a few studies. The article summarizes the current state of knowledge on the role of EDPs in the nervous system.

show abstract

The aryl hydrocarbon receptor and the gut–brain axis

Cited by 79 publications

References 155 publications

Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain

Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain

The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe

Elastin-Derived Peptides in the Central Nervous System: Friend or Foe

Contact Info

Product

Resources

About