Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis
Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis
复制标题
DOI：
10.1523/jneurosci.4781-03.2004
复制
发表时间：
2004-01-21
影响因子：
5.3
通讯作者：
Boison, D
中科院分区：
文献类型：
--
作者：
Gouder, N;Scheurer, L;Boison, D
大脑中的内源性腺苷被认为通过强直性抗惊厥作用来防止癫痫发作的发展和扩散。脑内腺苷水平主要受腺苷激酶活性的调节。为了建立腺苷激酶表达与癫痫发作活动之间的联系，我们分析了腺苷激酶在对照小鼠大脑和凯尼克酸诱导的小鼠内侧颞叶癫痫模型中的表达。对照小鼠脑切片的免疫组化分析显示，腺苷激酶染色强烈，主要在星形胶质细胞中，星形胶质细胞或多或少均匀地分布在整个大脑中，以及一些神经元，特别是嗅球、纹状体和脑干。相比之下，单侧kainic酸注射损伤的海马表现出严重的星形胶质细胞增生，因此腺苷激酶免疫反应性显著增加，伴随相应的酶活性增加，这与该脑区慢性复发性癫痫发作活动相一致。因此，通过注射低剂量的腺苷激酶抑制剂5-碘结核菌素抑制癫痫发作和间期尖峰。我们得出结论，腺苷激酶在癫痫海马的离散部分的过度表达可能有助于癫痫活动的发展和进展。
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.