Abstract
It is of great importance to explore the development of epileptogenesis, and the adenosine and adenosine kinase (ADK) system seems to play a key role in this process. The aim of this study is to explore the dynamic changes of astrocytes and adenosine signaling during epileptogenesis in rat hippocampus in a post-status epileptogenesis (SE) model. Rat SE models were built and killed for experiments at 1 day (acute phase of epileptogenesis), 5 days (latent phase), 4 weeks (chronic phase), and 8 weeks (late chronic phase of epileptogenesis) after SE induction. Immunofluorescence staining, high-performance liquid chromatography, and Western blotting were performed to assess changes of astrocytes, adenosine, ADK, and ADK receptors (including A1R, A2aR, A2bR, and A3R) in hippocampus. The expression level of glial fibrillary acidic protein significantly increased from latent to late chronic phase. The concentration of adenosine sharply increased in acute phase and gradually decreased in the remaining phases of post-SE, being significantly lower than in the control group in late chronic phase. Protein levels of A1R and A2aR in post-SE models increased in acute phase, whereas A2bR and A3R protein expression decreased in latent phase, chronic phase, and late chronic phase following post-SE epileptogenesis. Protein expression of ADK significantly increased during latent phase, chronic phase, and late chronic phase of post-SE epileptogenesis. In conclusion, the levels of adenosine and protein expression of A1R and A2R significantly increased during acute phase of post-SE. During the remaining phases of post-SE epileptogenesis, there was imbalance among astrocytes, adenosine, adenosine receptors, and ADK. Regulation of the ADK/adenosine system may provide potential treatment strategies for epileptogenesis.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (NSFC grant 81371452), Natural Science Foundation of Chongqing (CSTC 2013jjB0031; CSTC 2015jcyjA10091), Research Fund for the Doctoral Program of Higher Education of China (20125503110011), and Young and Middle-Age High-Level Medical Reserved Personnel Training Project Foundation of Chongqing.
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Hong, S., Li, T., Luo, Y. et al. Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis. Cell Mol Neurobiol 38, 1227–1234 (2018). https://doi.org/10.1007/s10571-018-0590-9
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DOI: https://doi.org/10.1007/s10571-018-0590-9