Dynamic changes of activated AHR in microglia and astrocytes in the substantia nigra-striatum system in an MPTP-induced Parkinson’s disease mouse model

Zhou, Yu; Zhao, Wenjin; Quan, Wei; Qiao, Chen-Meng; Cui, Chun; Hong, Hui; Shi, Yun; Niu, Gu-Yu; Zhao, Liping; Shen, Yan‐Qin

doi:10.1016/j.brainresbull.2021.08.013

Cited by 18 publications

(8 citation statements)

References 34 publications

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“…In the liver, xenobiotic metabolizing enzymes, cytochrome P450 and sulfotransferases convert indole into compounds such as indoxyl-3-sulfate (IS), oxindole and isatin [ 99 ]. Trp can also be degraded by intestinal bacteria to indole-3-propionic acid (IPA), indole-3-acetaldehyde (IAld), indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), tryptamine, indoleethanol (IE), indole-3-acetaldehyde (IAAld) or 3-methylindole (skatole) [ 100 ]. There are qualitative and quantitative differences in indole production among different people due to diverse gut microbiota species colonizing the gut.…”

Section: Tryptophan Metabolismmentioning

confidence: 99%

“…The data on the role of AhR in PD are, to our knowledge, limited to experimental animal research. In the MPTP-induced model, the number of AhR-positive microglial and glial cells in the striatum and the SNpc increased, whereas AhR-positive tyrosine-hydroxylase-expressing neurons were reduced [ 100 ]. In mice, the administration of the AhR ligand resulted in a twofold increase in protein levels of a ubiquitin-conjugating enzyme that interacts with parkin (UbcH7).…”

Section: Ahr In the Gut–brain Axismentioning

confidence: 99%

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Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

Iwaniak,

Owe-Larsson,

Urbańska

2024

IJMS

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In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson’s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut–brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota–Trp-KYN–brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research.

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Section: Tryptophan Metabolismmentioning

confidence: 99%

Section: Ahr In the Gut–brain Axismentioning

confidence: 99%

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

Iwaniak,

Owe-Larsson,

Urbańska

2024

IJMS

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“…By means of gene-deficient mice and the administration of AhR agonists and antagonists, numerous researchers have demonstrated that AhR modulates an immune response in various respiratory diseases and that lungs are sensitive to AhR ligands [ 279 , 280 , 281 ]. Allergic and inflammatory diseases such as bronchitis, asthma, and chronic obstructive pulmonary disease were recently linked with exposure to environmental toxic compounds.…”

Section: Ahr In the Pathogenesis Of Diseases Related To Oxidative Stressmentioning

confidence: 99%

Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance

Grishanova

Perepechaeva

2022

IJMS

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The aryl hydrocarbon receptor (AhR) has long been implicated in the induction of a battery of genes involved in the metabolism of xenobiotics and endogenous compounds. AhR is a ligand-activated transcription factor necessary for the launch of transcriptional responses important in health and disease. In past decades, evidence has accumulated that AhR is associated with the cellular response to oxidative stress, and this property of AhR must be taken into account during investigations into a mechanism of action of xenobiotics that is able to activate AhR or that is susceptible to metabolic activation by enzymes encoded by the genes that are under the control of AhR. In this review, we examine various mechanisms by which AhR takes part in the oxidative-stress response, including antioxidant and prooxidant enzymes and cytochrome P450. We also show that AhR, as a participant in the redox balance and as a modulator of redox signals, is being increasingly studied as a target for a new class of therapeutic compounds and as an explanation for the pathogenesis of some disorders.

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“…In contrast to TRP and kynurenine, serotonin does not cross the blood–brain barrier (BBB). Studies suggest that indole can also cross the BBB and exhibit pro-inflammatory activity by activating the aryl hydrocarbon receptor pathway in the astrocytes ( Ojo and Tischkau, 2021 ; Zhou et al, 2021 ; Huang et al, 2023 ). Two major pools of serotonin are recognized: 95% is the gut serotonin required for the regulation of intestinal homeostasis and predominantly produced by Clostridial species ( Yano et al, 2015 ; Fung et al, 2019 ), and nearly 5% corresponds to the serotonin produced by the host brain from TRP and serotonin ( Gostner et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring the interplay between running exercises, microbial diversity, and tryptophan metabolism along the microbiota-gut-brain axis

Vazquez-Medina,

Rodriguez-Trujillo,

Ayuso-Rodriguez

et al. 2024

Front. Microbiol.

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The emergent recognition of the gut-brain axis connection has shed light on the role of the microbiota in modulating the gut-brain axis’s functions. Several microbial metabolites, such as serotonin, kynurenine, tryptamine, indole, and their derivatives originating from tryptophan metabolism have been implicated in influencing this axis. In our study, we aimed to investigate the impact of running exercises on microbial tryptophan metabolism using a mouse model. We conducted a multi-omics analysis to obtain a comprehensive insight into the changes in tryptophan metabolism along the microbiota-gut-brain axis induced by running exercises. The analyses integrated multiple components, such as tryptophan changes and metabolite levels in the gut, blood, hippocampus, and brainstem. Fecal microbiota analysis aimed to examine the composition and diversity of the gut microbiota, and taxon-function analysis explored the associations between specific microbial taxa and functional activities in tryptophan metabolism. Our findings revealed significant alterations in tryptophan metabolism across multiple sites, including the gut, blood, hippocampus, and brainstem. The outcomes indicate a shift in microbiota diversity and tryptophan metabolizing capabilities within the running group, linked to increased tryptophan transportation to the hippocampus and brainstem through circulation. Moreover, the symbiotic association between Romboutsia and A. muciniphila indicated their potential contribution to modifying the gut microenvironment and influencing tryptophan transport to the hippocampus and brainstem. These findings have potential applications for developing microbiota-based approaches in the context of exercise for neurological diseases, especially on mental health and overall well-being.

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Dynamic changes of activated AHR in microglia and astrocytes in the substantia nigra-striatum system in an MPTP-induced Parkinson’s disease mouse model

Cited by 18 publications

References 34 publications

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance

Exploring the interplay between running exercises, microbial diversity, and tryptophan metabolism along the microbiota-gut-brain axis

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