ArticleBiological psychiatry2016
Microglial Acid Sensing Regulates Carbon Dioxide-Evoked Fear.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The role of acid-sensitive ion channels in panic disorder: a systematic review of animal studies and meta-analysis of human studies.Translational psychiatry · 2018Pooled it
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- Neuroimmune regulation of behavior: Focus on sensory circumventricular organs and associated cell circuit mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- ASIC1a channels in the locus coeruleus mediate hypercapnic acidosis detection and COPsychopharmacology · 2026Article
- A novel interoceptive subfornical organ to infralimbic cortex mechanism relays airway inflammation effects on fear extinction.Research square · 2026Article
- Sex differences in responses to panicogen COFrontiers in cellular neuroscience · 2026Article
- Projections from subfornical organ to bed nucleus of the stria terminalis modulate inflammation-induced anxiety-like behaviors in mice.Science advances · 2024Article
- Locus coeruleus noradrenaline depletion and its differential impact on COProgress in neuro-psychopharmacology & biological psychiatry · 2024Article
- Delayed Chronic Acidic Postconditioning Improves Poststroke Motor Functional Recovery and Brain Tissue Repair by Activating Proton-Sensing TDAG8.Translational stroke research · 2024Article
- Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice.Neurobiology of stress · 2024Article
- Article
- Editorial: Alternative and expanding views on central respiratory chemoreception in health and disease.Frontiers in physiology · 2024Article
- Microglial reactivity in brainstem chemosensory nuclei in response to hypercapnia.Frontiers in physiology · 2024Article
- Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways.Military Medical Research · 2023Article
- Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride.Science advances · 2023Article
- Altered Fear Behavior in Aeroallergen House Dust Mite Exposed C57Bl/6 Mice: A Model of Th2-skewed Airway Inflammation.Neuroscience · 2023Article
- Neuromedin B-Expressing Neurons in the Retrotrapezoid Nucleus Regulate Respiratory Homeostasis and Promote Stable Breathing in Adult Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder.Translational psychiatry · 2023Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCarbon dioxide (CO2) inhalation, a biological challenge and pathologic marker in panic disorder, evokes intense fear and panic attacks in susceptible individuals. The molecular identity and anatomic location of CO2-sensing systems that translate CO2-evoked fear remain unclear. We investigated contributions of microglial acid sensor T cell death-associated gene-8 (TDAG8) and microglial proinflammatory responses in CO2-evoked behavioral and physiological responses.
methodsCO2-evoked freezing, autonomic, and respiratory responses were assessed in TDAG8-deficient ((-/-)) and wild-type ((+/+)) mice. Involvement of TDAG8-dependent microglial activation and proinflammatory cytokine interleukin (IL)-1β with CO2-evoked responses was investigated using microglial blocker, minocycline, and IL-1β antagonist IL-1RA. CO2-chemosensitive firing responses using single-cell patch clamping were measured in TDAG8(-/-) and TDAG8(+/+) mice to gain functional insights.
resultsTDAG8 expression was localized in microglia enriched within the sensory circumventricular organs. TDAG8(-/-) mice displayed attenuated CO2-evoked freezing and sympathetic responses. TDAG8 deficiency was associated with reduced microglial activation and proinflammatory cytokine IL-1β within the subfornical organ. Central infusion of microglial activation blocker minocycline and IL-1β antagonist IL-1RA attenuated CO2-evoked freezing. Finally, CO2-evoked neuronal firing in patch-clamped subfornical organ neurons was dependent on acid sensor TDAG8 and IL-1β.
conclusionsOur data identify TDAG8-dependent microglial acid sensing as a unique chemosensor for detecting and translating hypercapnia to fear-associated behavioral and physiological responses, providing a novel mechanism for homeostatic threat detection of relevance to psychiatric conditions such as panic disorder.
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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.