Skip to content
DraconiticResearch
Search Sources API
184,584 studies31 sourcesUpdated 22 min ago
Peer-reviewedCC BY 4.0Cells

Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity

  • Cheng Yuan1
  • Jixin Chen1
  • Yazhi Chen1
  • Liyuan Cui2
  • Yingjiao Liu1
  1. 1College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China
  2. 2State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Read full textPDFDOICite

Abstract

Excitotoxicity constitutes a core pathological mechanism in cerebral ischemia and other central nervous system disorders. Astrocytes serve as pivotal regulators of glutamate–glutamine cycle homeostasis and thereby play a critical role in mitigating excitotoxicity. This study established a rat thromboembolic stroke model via autologous thrombus induction and systematically investigated the mechanisms underlying adenosine-mediated neuroprotection through pharmacological modulation of the adenosine pathway using adenosine, dipyridamole, and selective adenosine receptor antagonists. Subsequently, light-sensitive opsin expression in astrocytes was driven by the GFAP promoter, enabling cell-type-specific optogenetic modulation of astrocyte activity. Our findings demonstrate that adenosine significantly attenuates cerebral injury in a rat model of thromboembolic stroke, with astrocytes identified as the primary cellular target. Adenosine elicits an anti-excitotoxic effect by coordinately upregulating GLT-1 protein expression and downregulating Cx43 protein expression in astrocytes, thereby regulating glutamate transport and diffusion. Moreover, our findings demonstrate that adenosine-mediated neuroprotection is significantly attenuated by SCH58261 but not by PSB1115. We conclude that the adenosine–A2A receptor system plays a critical role in the regulation of glutamate homeostasis.

Related

  1. Enhancement of Endocannabinoid Signaling by Dual MAGL/ABHD6 Inhibition Reduces Neurodegeneration and Neuro-Inflammation Following AMPA-Mediated Excitotoxicity
    Dimitris Spyridakos, Ioannis Zyganitidis, Sofia Petsangouraki +6
    BiomoleculesPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossrefEurope PMC
  2. Extracellular adenosine triphosphate upregulates S100A4 expression and promotes the migration and invasion of breast cancer cells via P2Y2/SOX9 signaling
    Yue Cui, Fengming Ran, Guangxiong Ruan +2
    Translational cancer researchPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  3. N6-Substituted adenosine analogues, a novel class of JAK2 inhibitors, potently block STAT3 signaling in human cancer cells
    Peng Liu, Liwei Zhao, Ximing Xu +8
    Cancer LettersPeer-reviewedCC BY-NC10 citedOncologyHAL
  4. Caffeic acid mitigates myocardial fibrosis via suppressing MAPKs/CREB-mediated inflammation in myocardial ischemia-reperfusion injury mice.
    Mi Xiang, Xiaohu Ouyang, Shuxin Song +5
    Chinese medicinePeer-reviewedCC BYFull textCardiovascular medicineEurope PMCPMC
  5. Terahertz Photons Ameliorate Traumatic Brain Injury and Reduce Neuroinflammation via the Cyclic Adenosine Monophosphate Signaling Pathway.
    Jingzhou Liu, Xin Zhao, Yuan Zhong +7
    Research (Washington, D.C.)Peer-reviewedCC BYFull textNeurologyEurope PMCPMC

Cite

BibTeXRIS
BibTeX
@article{yuan2026adenosinea2,
  title = {{Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity}},
  author = {Cheng Yuan and Jixin Chen and Yazhi Chen and Liyuan Cui and Yingjiao Liu},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15201915},
  url = {https://www.mdpi.com/2073-4409/15/20/1915},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity
AU  - Cheng Yuan
AU  - Jixin Chen
AU  - Yazhi Chen
AU  - Liyuan Cui
AU  - Yingjiao Liu
PY  - 2026
DA  - 2026/10/21
JO  - Cells
DO  - 10.3390/cells15201915
UR  - https://www.mdpi.com/2073-4409/15/20/1915
AB  - Excitotoxicity constitutes a core pathological mechanism in cerebral ischemia and other central nervous system disorders. Astrocytes serve as pivotal regulators of glutamate–glutamine cycle homeostasis and thereby play a critical role in mitigating excitotoxicity. This study established a rat thromboembolic stroke model via autologous thrombus induction and systematically investigated the mechanisms underlying adenosine-mediated neuroprotection through pharmacological modulation of the adenosine pathway using adenosine, dipyridamole, and selective adenosine receptor antagonists. Subsequently, light-sensitive opsin expression in astrocytes was driven by the GFAP promoter, enabling cell-type-specific optogenetic modulation of astrocyte activity. Our findings demonstrate that adenosine significantly attenuates cerebral injury in a rat model of thromboembolic stroke, with astrocytes identified as the primary cellular target. Adenosine elicits an anti-excitotoxic effect by coordinately upregulating GLT-1 protein expression and downregulating Cx43 protein expression in astrocytes, thereby regulating glutamate transport and diffusion. Moreover, our findings demonstrate that adenosine-mediated neuroprotection is significantly attenuated by SCH58261 but not by PSB1115. We conclude that the adenosine–A2A receptor system plays a critical role in the regulation of glutamate homeostasis.
SN  - 2073-4409
ER  -