Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using
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ORIGINAL ARTICLE
Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse James Morgan1 • Mariana Alves1 • Giorgia Conte1 • Aida Mene´ndez-Me´ndez1 Laura de Diego-Garcia1 • Gioacchino de Leo1 • Edward Beamer1 • Jonathon Smith1,2 • Annette Nicke3 • Tobias Engel1,2
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Received: 3 March 2020 / Accepted: 8 July 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
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. Colocalization 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
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00573-9) contains supplementary material, which is available to authorized users. & Tobias Engel [email protected] 1
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland
2
FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland
3
Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universita¨t Mu¨nchen, 80336 Munich, Germany
contributing to brain inflammation and neurodegeneration following acute seizures and during epilepsy. Keywords Purinergic signaling P2X7 Green fluorescence protein Status epilepticus Epilepsy Cell typespecific expression
Introduction The purinergic family of receptors has garnered much attention as potential therapeutic drug targets for numerous human pathological conditions, particularly diseases of the central nervous system (CNS), such as epilepsy [1–3]. Epilepsy is a heterogeneous group of brain disorders with an incidence of 1%–2% and affects * 70 million people worldwide [4]. Despite the availability of [ 25 seizuresuppressing drugs, drug-refractoriness remains steadfast at * 30%, and, even if seizure-suppressive, current pharmacological interventions are merely symptomatic without significantly altering the progression of the disease [5
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