Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis

被引:176
作者
Gouder, N
Scheurer, L
Fritschy, JM
Boison, D
机构
[1] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
[2] Fed Inst Technol ETH, Dept Chem & Appl Biosci, CH-8057 Zurich, Switzerland
关键词
adenosine kinase; adenosine; epilepsy; seizure susceptibility; kainic acid; iodotubercidin;
D O I
10.1523/JNEUROSCI.4781-03.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Endogenous adenosine in the brain is thought to prevent the development and spread of seizures via a tonic anticonvulsant effect. Brain levels of adenosine are primarily regulated by the activity of adenosine kinase. To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy. Immunohistochemical analysis of brain sections of control mice revealed intense staining for adenosine kinase, mainly in astrocytes, which were more or less evenly distributed throughout the brain, as well as in some neurons, particularly in olfactory bulb, striatum, and brainstem. In contrast, hippocampi lesioned by a unilateral kainic acid injection displayed profound astrogliosis and therefore a significant increase in adenosine kinase immunoreactivity accompanied by a corresponding increase of enzyme activity, which paralleled chronic recurrent seizure activity in this brain region. Accordingly, seizures and interictal spikes were suppressed by the injection of a low dose of the adenosine kinase inhibitor 5-iodotubercidin. We conclude that overexpression of adenosine kinase in discrete parts of the epileptic hippocampus may contribute to the development and progression of seizure activity.
引用
收藏
页码:692 / 701
页数:10
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