Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2014.00312
Keywords
deep brain stimulation; epilepsy; thalamus; anterior nucleus; seizures; adenosine
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Funding
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2011150680-2, 50950-2]
- Fapemig (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- AFIP (Associacao Fundo de Incentivo a Pesquisa)
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Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiforrn activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.
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