Abstract
Epileptic seizures are caused by an electrical disturbance of brain activity that results in abnormal and excessive synchronization of neurons. Adenosine is a long-known anticonvulsant endogenous substance, exerting its actions through diverse mechanisms of action at different cellular targets. In this review we discuss the main actions of adenosine during acute and chronic phases of epileptic seizure progression and the mechanisms involved. There should be considered three main levels of adenosine actions: (1) neuronal level, where adenosine, mostly through its receptors A1, A2A and A3, alters intrinsic neuronal properties and excitatory/inhibitory network balance; (2) non-neuronal level, by affecting astrocytic function; and (3) homeostatic control level, through epigenetic regulatory mechanisms. Together, these actions make adenosine as a sort of “universal modulator or maestro” of desynchronization of epileptic focus, with great therapeutic potential in the treatment of resistant forms of epileptic seizures. Indeed, adenosine augmentation therapies are being considered to tackle epilepsy, which include gene therapy strategies and dietary interventions. Further research on new drugs that specifically target the mechanisms of actions involved in the pathological process of the disease are needed to take full advantage of adenosine anticonvulsant actions in the control of epileptic seizures.
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Acknowledgements
The research carried out by the authors of this work have been supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia (FCT), by an FCT project (PTDC/DTP-FTO/3346/2014) and by Twinning action (SynaNet) from the EU H2020 programme (project number: 692340).
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Rombo, D.M., Ribeiro, J.A., Sebastião, A.M. (2018). Role of Adenosine Receptors in Epileptic Seizures. In: Borea, P., Varani, K., Gessi, S., Merighi, S., Vincenzi, F. (eds) The Adenosine Receptors. The Receptors, vol 34. Humana Press, Cham. https://doi.org/10.1007/978-3-319-90808-3_13
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