Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2Y1 Receptor in Experimental Epilepsy
journal contributionposted on 10.07.2020 by Mariana Alves, Laura De Diego Garcia, Giorgia Conte, Eva M. Jimenez-Mateos, Beatrice D’Orsi, Amaya Sanz Rodriguez, Jochen Prehn, David Henshall, Tobias Engel
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This is the first study to fully characterize the contribution of a metabotropic purinergic P2Y receptor during acute seizures and epilepsy. The findings suggest that targeting P2Y1 may offer a potential novel treatment strategy for drug-refractory status epilepticus and epilepsy. Our data demonstrate a context-specific role of P2Y1 activation during seizures, switching from a proconvulsiveto an anticonvulsive role depending on physiopathological context. Thus, our study provides a possible explanation for seemingly conflicting results obtained between studies of different brain diseases where P2Y1 targeting has been proposed as a potential treatment strategy and highlights that the timing of pharmacological interventions is of critical importance to the understanding of how receptors contribute to the generation of seizures and the development of epilepsy.
This work was supported by funding from the Health Research Board HRA-POR-2015-1243 to TE); Science Foundation Ireland (13/SIRG/2098 and 17/CDA/4708 to T.E, 13/SIRG/2114 to EJ and co-funded under the European Regional Development Fund and by FutureNeuro industry partners 16/RC/3948 to DCH); from the H2020 Marie Skłowdowksa-Curie Actions Individual Fellowship (796600 to LD) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklowdowska-Cuire grant agreement (No. 766124 to T.E.). The authors would like to thank Dr. Heiko Duessmann for assistance with confocal microscopy. Funding statement The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
CommentsThis article is also available at https://www.jneurosci.org/
Published CitationAlves M, Diego Garcia LD, Conte G, Jimenez-Mateos EM, D’Orsi B, Rodriguez AS, Prehn J, Henshall D, Engel T. Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2Y1 Receptor in Experimental Epilepsy. The Journal of Neuroscience. 2019;39(27):5377-5392
- Physiology and Medical Physics
- Neurological and Psychiatric Disorders