Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse

Abstract

Mounting evidence suggests that the ATP-gated P2X7 receptor contributes to increased hyperexcitability in the brain. While increased expression of P2X7 in the hippocampus and cortex following status epilepticus and during epilepsy has been repeatedly demonstrated, the cell type-specific expression of P2X7 and its expression in extra-hippocampal brain structures remains incompletely explored. In this study, P2X7 expression was visualized by using a transgenic mouse model overexpressing P2X7 fused to the fluorescent protein EGFP. The results showed increased P2X7-EGFP expression after status epilepticus induced by intra-amygdala kainic acid and during epilepsy in different brain regions including the hippocampus, cortex, striatum, thalamus and cerebellum, and this was most evident in microglia and oligodendrocytes. Co-localization of P2X7-EGFP with cell type-specific markers was not detected in neurons or astrocytes. These data suggest that P2X7 activation is a common pathological hallmark across different brain structures, possibly contributing to brain inflammation and neurodegeneration following acute seizures and during epilepsy.

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Acknowledgements

This work was supported by funding from the Health Research Board (HRA-POR-2015-1243), the Science Foundation Ireland (17/CDA/4708 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners 16/RC/3948), H2020 Marie Skłodowksa-Curie Actions Individual Fellowships (753527, 796600 and 844956), the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (766124), and the Deutsche Forschungsgemeinschaft (German Research Foundation; Project-ID 335447717 - SFB 1328).

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Morgan, J., Alves, M., Conte, G. et al. Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse. Neurosci. Bull. (2020). https://doi.org/10.1007/s12264-020-00573-9

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Keywords

  • Purinergic signaling
  • P2X7
  • Green fluorescence protein
  • Status epilepticus
  • Epilepsy
  • Cell type-specific expression