ArticleScientific reports2017
α7 nicotinic acetylcholine receptor signaling modulates the inflammatory phenotype of fetal brain microglia: first evidence of interference by iron homeostasis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- A Humanized Knock-in Mouse Model of the PSEN1 V97L Mutation from a Major Chinese Alzheimer's Disease Pedigree Reveals Early Neuroinflammation.Neuroscience bulletin · 2026Article
- Unraveling Neurodevelopment: Synergistic Effects of Intrinsic Genetic Programs and Extrinsic Environmental Cues.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Effects of prenatal iron deficiency on neurological development and related disorders in offspring.Frontiers in nutrition · 2025Review
- Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest.Journal of inflammation research · 2025Article
- Microglial and Macrophage Plasticity and Regional Cerebral Blood Flow in the Prenatal Brain and Gut Under Vagus Nerve Stimulation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation.International journal of molecular sciences · 2024Review
- The Vagus Nerve Regulates Immunometabolic Homeostasis in the Ovine Fetus near Term: The Impact on Terminal Ileum.Biology · 2024Article
- Autism Spectrum Disorder: A Neuro-Immunometabolic Hypothesis of the Developmental Origins.Biology · 2023Article
- Prenatal stress perturbs fetal iron homeostasis in a sex specific manner.Scientific reports · 2022Article
- Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3.Molecules (Basel, Switzerland) · 2021Review
- The selective alpha7 nicotinic acetylcholine receptor agonist AR-R17779 does not affect ischemia-reperfusion brain injury in mice.Bioscience reports · 2021Article
- Uncovering sex differences of rodent microglia.Journal of neuroinflammation · 2021Review
- Changing Functional Signatures of Microglia along the Axis of Brain Aging.International journal of molecular sciences · 2021Review
- A Translational Perspective of Maternal Immune Activation by SARS-CoV-2 on the Potential Prenatal Origin of Neurodevelopmental Disorders: The Role of the Cholinergic Anti-inflammatory Pathway.Frontiers in psychology · 2021Article
- Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood.Neuroscience and biobehavioral reviews · 2020Review
- Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation.Frontiers in cellular neuroscience · 2020Review
- α7 Nicotinic Acetylcholine Receptor Signaling Modulates Ovine Fetal Brain Astrocytes Transcriptome in Response to Endotoxin.Frontiers in immunology · 2019Article
- Electroacupuncture Pretreatment Alleviates Cerebral Ischemic Injury Through α7 Nicotinic Acetylcholine Receptor-Mediated Phenotypic Conversion of Microglia.Frontiers in cellular neuroscience · 2019Article
- Systemic Immune Dyshomeostasis Model and Pathways in Alzheimer's Disease.Frontiers in aging neuroscience · 2019Article
- Alpha7 nAChR Expression Is Correlated with Arthritis Development and Inhibited by Sinomenine in Adjuvant-Induced Arthritic Rats.Evidence-based complementary and alternative medicine : eCAM · 2019Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation in utero may result in life-long neurological disabilities. Microglia play a pivotal role, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of microglia. We hypothesized that agonism on α7 nicotinic acetylcholine receptor (α7nAChR) in fetal microglia will augment their neuroprotective transcriptome profile, while the antagonistic stimulation of α7nAChR will achieve the opposite. Using an in vivo - in vitro model of developmental programming of neuroinflammation induced by lipopolysaccharide (LPS), we validated this hypothesis in primary fetal sheep microglia cultures re-exposed to LPS in presence of a selective α7nAChR agonist or antagonist. Our RNAseq and protein level findings show that a pro-inflammatory microglial phenotype acquired in vitro by LPS stimulation is reversed with α7nAChR agonistic stimulation. Conversely, antagonistic α7nAChR stimulation potentiates the pro-inflammatory microglial phenotype. Surprisingly, under conditions of LPS double-hit an interference of a postulated α7nAChR - ferroportin signaling pathway may impede this mechanism. These results suggest a therapeutic potential of α7nAChR agonists in early re-programming of microglia in neonates exposed to in utero inflammation via an endogenous cerebral cholinergic anti-inflammatory pathway. Future studies will assess the role of interactions between inflammation-triggered microglial iron sequestering and α7nAChR signaling in neurodevelopment.
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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.