ArticleMolecular neurobiology2016
Selective Aryl Hydrocarbon Receptor Modulator 3,3'-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.Pharmacological reports : PR · 2026Article
- Article
- The Aryl Hydrocarbon Receptor in Neurotoxicity: An Intermediator Between Dioxins and Neurons in the Brain.Toxics · 2025Review
- Enhancing Nutraceutical Efficacy: The Role of M.A.T.R.I.S. Technology in Modulating Intestinal Release of Lipoic Acid and L-Carnitine.International journal of molecular sciences · 2025Article
- Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.Plants (Basel, Switzerland) · 2025Review
- 3,3'-Diindolylmethane improves pathology and neurological outcome following traumatic brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- A dynamic model of gene activation in response to hypoxia accounting for both HIF-1 and HIF-2.Briefings in functional genomics · 2025Article
- Therapeutic Potential of Nutritional Aryl Hydrocarbon Receptor Ligands in Gut-Related Inflammation and Diseases.Biomedicines · 2024Review
- Posttreatment with PaPE-1 Protects from Aβ-Induced Neurodegeneration Through Inhibiting the Expression of Alzheimer's Disease-Related Genes and Apoptosis Process That Involves Enhanced DNA Methylation of Specific Genes.Molecular neurobiology · 2024Article
- Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.Frontiers in immunology · 2024Review
- Posttreatment with Ospemifene Attenuates Hypoxia- and Ischemia-Induced Apoptosis in Primary Neuronal Cells via Selective Modulation of Estrogen Receptors.Neurotoxicity research · 2023Article
- Intestinal epithelium aryl hydrocarbon receptor is involved in stress sensitivity and maintaining depressive symptoms.Behavioural brain research · 2023Article
- Amorfrutin B Protects Mouse Brain Neurons from Hypoxia/Ischemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation.Molecular neurobiology · 2023Article
- Sex-dependent differences in the stress mitigating and antidepressant effects of selective aryl hydrocarbon receptor modulators.Journal of affective disorders · 2022Article
- From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms.International journal of molecular sciences · 2022Review
- A Multimodal MR Imaging Study of the Effect of Hippocampal Damage on Affective and Cognitive Functions in a Rat Model of Chronic Exposure to a Plateau Environment.Neurochemical research · 2022Article
- 3,3'-diindolylmethane inhibits LPS-induced human chondrocytes apoptosis and extracellular matrix degradation by activating PI3K-Akt-mTOR-mediated autophagy.Frontiers in pharmacology · 2022Article
- Nuclear Receptors in Myocardial and Cerebral Ischemia-Mechanisms of Action and Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Neuroprotective effect of 3,3'-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes.Apoptosis : an international journal on programmed cell death · 2020Article
- Does kynurenic acid act on nicotinic receptors? An assessment of the evidence.Journal of neurochemistry · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuroprotective potential of 3,3'-diindolylmethane (DIM), which is a selective aryl hydrocarbon receptor modulator, has recently been shown in cellular and animal models of Parkinson's disease and lipopolysaccharide-induced inflammation. However, there are no data concerning the protective capacity and mechanisms of DIM action in neuronal cells exposed to hypoxia. The aim of the present study was to investigate the neuroprotective potential of DIM against the hypoxia-induced damage in mouse hippocampal cells in primary cultures, with a particular focus on DIM interactions with the aryl hydrocarbon receptor (AhR), its nuclear translocator ARNT, and estrogen receptor β (ERβ). In the present study, 18 h of hypoxia induced apoptotic processes, in terms of the mitochondrial membrane potential, activation of caspase-3, and fragmentation of cell nuclei. These effects were accompanied by substantial lactate dehydrogenase release and neuronal cell death. The results of the present study demonstrated strong neuroprotective and anti-apoptotic actions of DIM in hippocampal cells exposed to hypoxia. In addition, DIM decreased the Ahr and Arnt mRNA expression and stimulated Erβ mRNA expression level. DIM-induced mRNA alterations were mirrored by changes in protein levels, except for ERβ, as detected by ELISA, Western blotting, and immunofluorescence labeling. We also demonstrated that DIM decreased the expression of AhR-regulated CYP1A1. Using specific siRNAs, we provided evidence that impairment of AhR and ARNT, but not ERβ plays a key role in the neuroprotective action of DIM against hypoxia-induced cell damage. This study may have implication for identifying new agents that could protect neurons against hypoxia by targeting AhR/ARNT signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.