ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
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- Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability.Cell communication and signaling : CCS · 2025Article
- Nucleic acid sensing in the central nervous system: Implications for neural circuit development, function, and degeneration.Immunological reviews · 2024Review
- MiR-100-5p-rich small extracellular vesicles from activated neuron to aggravate microglial activation and neuronal activity after stroke.Journal of nanobiotechnology · 2024Article
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Let-7b-TLR7 Signaling Axis Contributes to the Anesthesia/Surgery-Induced Cognitive Impairment.Molecular neurobiology · 2024Article
- miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury.Cells · 2024Article
- The Sixth Sense: Self-nucleic acid sensing in the brain.Advances in immunology · 2024Review
- Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery.Frontiers in cellular neuroscience · 2024Review
- Counting the Toll of Inflammation on Schizophrenia-A Potential Role for Toll-like Receptors.Biomolecules · 2023Review
- Biomarker prediction in autism spectrum disorder using a network-based approach.BMC medical genomics · 2023Article
- High-throughput morphometric and transcriptomic profiling uncovers composition of naïve and sensory-deprived cortical cholinergic VIP/CHAT neurons.The EMBO journal · 2023Article
- A comprehensive study to delineate the role of an extracellular vesicle-associated microRNA-29a in chronic methamphetamine use disorder.Journal of extracellular vesicles · 2021Article
- Toll-like Receptors in Viral Encephalitis.Viruses · 2021Review
- Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis.Brain sciences · 2021Review
- TLR7 is expressed by support cells, but not sensory neurons, in ganglia.Journal of neuroinflammation · 2021Article
- Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders.Nature reviews. Immunology · 2021Review
- Article
- Potential value of pharmacological agents acting on toll-like receptor (TLR) 7 and/or TLR8 in COVID-19.Current research in pharmacology and drug discovery · 2021Review
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
Toll-like receptors (TLRs) recognize both pathogen- and danger-associated molecular patterns and induce innate immune responses. Some TLRs are expressed in neurons and regulate neurodevelopment and neurodegeneration. However, the downstream signaling pathways and effectors for TLRs in neurons are still controversial. In this report, we provide evidence that TLR7 negatively regulates dendrite growth through the canonical myeloid differentiation primary response gene 88 (Myd88)-c-Fos-interleukin (IL)-6 pathway. Although both TLR7 and TLR8 recognize single-stranded RNA (ssRNA), the results of quantitative reverse transcription-PCR suggested that TLR7 is the major TLR recognizing ssRNA in brains. In both in vitro cultures and in utero electroporation experiments, manipulation of TLR7 expression levels was sufficient to alter neuronal morphology, indicating the presence of intrinsic TLR7 ligands. Besides, the RNase A treatment that removed ssRNA in cultures promoted dendrite growth. We also found that the addition of ssRNA and synthetic TLR7 agonists CL075 and loxoribine, but not R837 (imiquimod), to cultured neurons specifically restricted dendrite growth via TLR7. These results all suggest that TLR7 negatively regulates neuronal differentiation. In cultured neurons, TLR7 activation induced IL-6 and TNF-α expression through Myd88. Using Myd88-, IL-6-, and TNF-α-deficient neurons, we then demonstrated the essential roles of Myd88 and IL-6, but not TNF-α, in the TLR7 pathway to restrict dendrite growth. In addition to neuronal morphology, TLR7 knockout also affects mouse behaviors, because young mutant mice ∼2 weeks of age exhibited noticeably lower exploratory activity in an open field. In conclusion, our study suggests that TLR7 negatively regulates dendrite growth and influences cognition in mice.
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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.