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首页> 外文期刊>The European Journal of Neuroscience >Acetylcholine-induced seizure-like activity and modified cholinergic gene expression in chronically epileptic rats.
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Acetylcholine-induced seizure-like activity and modified cholinergic gene expression in chronically epileptic rats.

机译：在慢性癫痫大鼠中乙酰胆碱诱导的癫痫样活动和修饰的胆碱能基因表达。

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摘要

The entorhinal cortex (EC) plays an important role in temporal lobe epilepsy. Under normal conditions, the enriched cholinergic innervation of the EC modulates local synchronized oscillatory activity; however, its role in epilepsy is unknown. Enhanced neuronal activation has been shown to induce transcriptional changes of key cholinergic genes and thus alter cholinergic responses. To examine cholinergic modulations in epileptic tissue we studied molecular and electrophysiological cholinergic responses in the EC of chronically epileptic rats following exposure to pilocarpine or kainic acid. We confirmed that while the total activity of the acetylcholine (ACh)-hydrolysing enzyme, acetylcholinesterase (AChE) was not altered, epileptic rats showed alternative splicing of AChE pre-mRNA transcripts, accompanied by a shift from membrane-bound AChE tetramers to soluble monomers. This was associated with increased sensitivity to ACh application: thus, in control rats, ACh (10-100 microm) induced slow (< 1Hz), periodic events confined to the EC; however, in epileptic rats, ACh evoked seconds-long seizure-like events with initial appearance in the EC, and frequent propagation to neighbouring cortical regions. ACh-induced seizure-like events could be completely blocked by the non-specific muscarinic antagonist, atropine, and were partially blocked by the muscarinic-1 receptor antagonist, pirenzepine; but were not affected by the non-specific nicotinic antagonist, mecamylamine. Epileptic rats presented reduced transcript levels of muscarinic receptors with no evidence of mRNA editing or altered mRNA levels for nicotinic ACh receptors. Our findings suggest that altered cholinergic modulation may initiate seizure events in the epileptic temporal cortex.
机译：内嗅皮层（EC）在颞叶癫痫中起重要作用。在正常情况下，EC的丰富胆碱能神经支配可调节局部同步振荡活动。然而，其在癫痫中的作用尚不清楚。已显示增强的神经元活化可诱导关键胆碱能基因的转录变化，从而改变胆碱能反应。为了检查癫痫组织中的胆碱能调节，我们研究了慢性癫痫大鼠暴露于毛果芸香碱或海藻酸后在EC中的分子和电生理胆碱能反应。我们确认，虽然乙酰胆碱（ACh）水解酶，乙酰胆碱酯酶（AChE）的总活性没有改变，但癫痫大鼠显示AChE pre-mRNA转录物的选择性剪接，并伴随着膜结合AChE四聚体向可溶性单体的转变。这与增加对ACh的敏感性有关：因此，在对照大鼠中，ACh（10-100 microm）诱导了缓慢的（<1Hz）周期性事件局限于EC;然而，在癫痫大鼠中，ACh诱发了数秒钟的癫痫样发作，最初出现在EC中，并频繁传播到邻近的皮质区域。非特异性毒蕈碱拮抗剂阿托品可完全阻断ACh诱发的癫痫样事件，而毒蕈碱1受体拮抗剂哌仑西平可部分阻断ACh诱发的癫痫发作。但不受非特异性烟碱拮抗剂美卡敏的影响。癫痫大鼠的毒蕈碱受体的转录水平降低了，没有烟碱乙酰胆碱受体的mRNA编辑或mRNA水平改变的证据。我们的发现表明，胆碱能调节的改变可能会引起癫痫颞皮的癫痫发作。

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