ArticlePLoS biology2021
Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
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- Transcriptomic Profiling in Aged Mice Reveals an Association Between Sevoflurane Anesthesia and Neurocognitive Dysfunction.Cellular and molecular neurobiology · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Effects of GABAAR modulators CL218872 and MRK-016 on neural repair and synaptic plasticity in mice with Intracerebral hemorrhage.PloS one · 2026Article
- Sex-Specific Differences in the Secretome of Oligodendrocyte Progenitor Cells Post Hyperoxic Stress.Journal of extracellular biology · 2025Article
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- A nomogram for predicting cancer-related cognitive impairment in lung cancer patients from a nursing science precision health model perspective.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Assessing the causal effect of inflammation-related genes on myocarditis: A Mendelian randomization study.ESC heart failure · 2025Article
- Establishment of reference intervals for complete blood count in healthy adults at different altitudes on the Western Sichuan Plateau.Frontiers in medicine · 2025Article
- Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids.Frontiers in neuroscience · 2025Review
- Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Sensorineural hearing loss and cognitive impairment: three hypotheses.Frontiers in aging neuroscience · 2024Review
- Modeling Red Blood Cell Metabolism in the Omics Era.Metabolites · 2023Review
- Red Blood Cell Metabolism In Vivo and In Vitro.Metabolites · 2023Review
- Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.Neurology international · 2023Review
- Screening of activators of 2,3-diphosphoglycerate mutase from traditional Chinese herb medicines.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte-specific ADORA2B (eAdora2b-/-) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b-/- mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B-BPGM axis is a key component for anti-aging and anti-age-related functional decline.
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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.