Seizure-induced 5-HT release and chronic impairment of serotonergic function in rats
Seizure-induced 5-HT release and chronic impairment of serotonergic function in rats
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DOI：
10.1016/j.neulet.2012.12.007
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发表时间：
2013-02-08
影响因子：
2.5
通讯作者：
Lin, Ji-lan
中科院分区：
文献类型：
--
作者：
Lin, Wan-hui;Huang, Hua-pin;Lin, Ji-lan
本文分析了癫痫大鼠海马区5-羟色胺(5-HT)及其主要代谢物5-羟基吲哚乙酸(5-HIAA)的动态变化。大鼠全身注射毛果芸香碱(320 mg/kg)诱发癫痫发作。脑电记录发现，匹罗卡品注射后30min即可诱发出首次惊厥放电，癫痫持续状态(SE)发作后14d复发性放电达到高峰。在SE前、后不同时间点，用微透析法采集清醒动物海马区细胞外液。用高效液相色谱-电化学法测定样品中5-羟色胺和5-羟吲哚乙酸的含量。有趣的是，在SE后的30分钟内，海马区的5-羟色胺水平显著升高。SE后4d恢复至基础水平，7d继续降至基础水平的48%，14d降至基础水平的28%。相应地，在SE后2d，海马区5-HIAA开始显著升高，然后逐渐下降到低于基线水平。为了确定中缝核团(大脑中释放5-羟色胺的主要来源)中的5-羟色胺能神经元，对大脑切片进行色氨酸羟基酶(TPH)免疫组织化学染色。SE后28d，TPH阳性神经元数量和染色强度明显减少。这些数据表明，匹罗卡品导致海马区5-羟色胺的耗竭，并显著损害中缝核团中的5-羟色胺能神经元。5-羟色胺能功能的丧失可能在癫痫的病理生理学中起重要作用。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
We analyzed the dynamic concentration change of serotonin (5-HT) and its main metabolite 5-hydroxyindoleacetic acid (5-HIAA) within the epileptic hippocampus in rats. Seizure was induced by systemic injection of pilocarpine (320 mg/kg, i.p.). Using electroencephalography (EEG) recordings, we found that primary seizure discharge was induced 30 min after pilocarpine administration and that recurrent discharge peaked 14d after the onset of status epilepticus (SE). The extracellular fluid in the hippocampus was sampled by microdialysis from conscious animals at various time points before and after SE. The concentrations of 5-HT and 5-HIAA in the samples were measured by high-performance liquid chromatography and electrochemical detection (HPLC-ECD). Interestingly, 5-HT levels in the hippocampus were dramatically increased within the 30 min following SE. This reversed to basal level by 4d after SE and continued to drop to 48% at 7d and 28% of basal level 14d after SE. Accordingly, a marked increase of 5-HIAA in the hippocampus appeared at 2d after SE, then gradually declined to levels below baseline. To identify serotonergic neurons in the raphe nuclei (a major source of 5-HT release in the brain), brain sections were immunostained for tryptophan hydroxylase (TPH). The number of TPH positive neurons and the intensity of TPH staining significantly decreased at 28d after SE. These data suggest that pilocarpine induces depletion of 5-HT in the hippocampus and significantly compromise serotonergic neurons in the raphe nuclei. The loss of serotonergic function may play a significant role in the pathophysiology of epilepsy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.