Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2Y1 Receptor in Experimental Epilepsy.pdf (6.19 MB)
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journal contribution
posted on 2020-07-10, 14:14 authored by Mariana AlvesMariana Alves, Laura De Diego Garcia, Giorgia Conte, Eva M. Jimenez-Mateos, Beatrice D’Orsi, Amaya Sanz RodriguezAmaya Sanz Rodriguez, Jochen PrehnJochen Prehn, David HenshallDavid Henshall, Tobias EngelTobias EngelThis 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):5377-5392Publication Date
2019-07-03External DOI
PubMed ID
31048325Department/Unit
- Physiology and Medical Physics
Research Area
- Neurological and Psychiatric Disorders