Circulating P2X7 receptor signaling components as diagnostic biomarkers for temporal lobe epilepsy

  • Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.
Author:Giorgia Conte, Aida Menéndez-Méndez, Sebastian BauerORCiDGND, Hany El-Naggar, Mariana Alves, Annette Nicke, Norman Delanty, Felix RosenowORCiDGND, David C. HenshallORCiD, Tobias EngelORCiD
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/09/16
Date of first Publication:2021/09/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/03
Tag:P2X7 receptor; biomarkers; diagnosis; epilepsy; inflammation; psychogenic non-epileptic seizures; status epilepticus
Issue:9, art. 2444
Page Number:17
First Page:1
Last Page:17
This work was supported by funding from Science Foundation Ireland (17/CDA/4708 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners 16/RC/3948) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (No 766124), from the Irish Research Council (Government of Ireland Postdoctoral Fellowship Programme GOIPD/2020/865), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Project-ID: 335447717-SFB 1328 (A15), and from the H2020 Marie Skłodowska-Curie Actions Individual Fellowship (No 884956).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0