Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures
Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6...
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Published in | PloS one Vol. 8; no. 6; p. e67060 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
25.06.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N(6)-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy. |
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Bibliography: | Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: JZ GL ML. Performed the experiments: ML RK. Analyzed the data: ML RK JZ. Contributed reagents/materials/analysis tools: JS JZ. Wrote the paper: ML JZ. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0067060 |