Role of adenosine in the antiepileptic effects of deep brain stimulation
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 hypothes...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-10-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00312/full |
| _version_ | 1819056853490860032 |
|---|---|
| author | Maisa eMiranda Clement eHamani Clement eHamani Antonio-Carlos eAlmeida Beatriz eAmorim Carlos eMacedo Maria Jose eFernandes Jose eNobrega Mayra eAarao Ana Paula eAntonio Antonio eRodrigues Monica L Andersen Sergio eTufik Luiz E Mello Luciene eCovolan |
| author_facet | Maisa eMiranda Clement eHamani Clement eHamani Antonio-Carlos eAlmeida Beatriz eAmorim Carlos eMacedo Maria Jose eFernandes Jose eNobrega Mayra eAarao Ana Paula eAntonio Antonio eRodrigues Monica L Andersen Sergio eTufik Luiz E Mello Luciene eCovolan |
| author_sort | Maisa eMiranda |
| collection | DOAJ |
| description | 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 five days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform 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 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. |
| first_indexed | 2024-12-21T13:30:01Z |
| format | Article |
| id | doaj.art-7b999f320e73434bbbde4925ab5b9eb6 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-21T13:30:01Z |
| publishDate | 2014-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-7b999f320e73434bbbde4925ab5b9eb62022-12-21T19:02:20ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-10-01810.3389/fncel.2014.00312110605Role of adenosine in the antiepileptic effects of deep brain stimulationMaisa eMiranda0Clement eHamani1Clement eHamani2Antonio-Carlos eAlmeida3Beatriz eAmorim4Carlos eMacedo5Maria Jose eFernandes6Jose eNobrega7Mayra eAarao8Ana Paula eAntonio9Antonio eRodrigues10Monica L Andersen11Sergio eTufik12Luiz E Mello13Luciene eCovolan14Universidade Federal de São João del-ReiUniversity of TorontoCentre for Addiction and Mental HealthUniversidade Federal de São João del-ReiUniversidade Federal de São PauloUniversidade Federal de São PauloUniversidade Federal de São PauloCentre for Addiction and Mental HealthUniversidade Federal de São João del-ReiUniversidade Federal de São João del-ReiUniversidade Federal de São João del-ReiUniversidade Federal de São PauloUniversidade Federal de São PauloUniversidade Federal de São PauloUniversidade Federal de São PauloDespite 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 five days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform 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 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.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00312/fullAdenosineDeep Brain StimulationEpilepsySeizuresThalamusanterior nucleus |
| spellingShingle | Maisa eMiranda Clement eHamani Clement eHamani Antonio-Carlos eAlmeida Beatriz eAmorim Carlos eMacedo Maria Jose eFernandes Jose eNobrega Mayra eAarao Ana Paula eAntonio Antonio eRodrigues Monica L Andersen Sergio eTufik Luiz E Mello Luciene eCovolan Role of adenosine in the antiepileptic effects of deep brain stimulation Frontiers in Cellular Neuroscience Adenosine Deep Brain Stimulation Epilepsy Seizures Thalamus anterior nucleus |
| title | Role of adenosine in the antiepileptic effects of deep brain stimulation |
| title_full | Role of adenosine in the antiepileptic effects of deep brain stimulation |
| title_fullStr | Role of adenosine in the antiepileptic effects of deep brain stimulation |
| title_full_unstemmed | Role of adenosine in the antiepileptic effects of deep brain stimulation |
| title_short | Role of adenosine in the antiepileptic effects of deep brain stimulation |
| title_sort | role of adenosine in the antiepileptic effects of deep brain stimulation |
| topic | Adenosine Deep Brain Stimulation Epilepsy Seizures Thalamus anterior nucleus |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00312/full |
| work_keys_str_mv | AT maisaemiranda roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT clementehamani roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT clementehamani roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT antoniocarlosealmeida roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT beatrizeamorim roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT carlosemacedo roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT mariajoseefernandes roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT joseenobrega roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT mayraeaarao roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT anapaulaeantonio roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT antonioerodrigues roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT monicalandersen roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT sergioetufik roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT luizemello roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation AT lucieneecovolan roleofadenosineintheantiepilepticeffectsofdeepbrainstimulation |