Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2Y1 Receptor in Experimental Epilepsy.pdf (6.19 MB)

Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2Y1 Receptor in Experimental Epilepsy

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posted on 10.07.2020, 14:14 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
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.

Funding

Health Research Board HRA-POR-2015-12

Science Foundation Ireland (13/SIRG/2098; 17/CDA/4708; 13/SIRG/2114)

European Regional Development Fund

FutureNeuro industry partners 16/RC/3948

H2020 Marie Skłowdowksa-Curie Actions Individual Fellowship (796600)

European Union’s Horizon 2020 research and innovation programme under the Marie Sklowdowska-Cuire grant agreement (No. 766124)

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This article is also available at https://www.jneurosci.org/

Published Citation

Alves 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

Publication Date

2019-07-03

PubMed ID

31048325

Department/Unit

  • Physiology and Medical Physics

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Society for Neuroscience

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Royal College of Surgeons in Ireland

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