Harmful blooms of domoic acid (DA)-producing algae are a problem in oceans worldwide. DA is a potent glutamate receptor agonist that can cause status epilepticus and in survivors, temporal lobe epilepsy. In mice, one-time low-dose in utero exposure to DA was reported to cause hippocampal damage and epileptiform activity, leading to the hypothesis that unrecognized exposure to DA from contaminated seafood in pregnant women can damage the fetal hippocampus and initiate temporal lobe epileptogenesis. However, development of epilepsy (i.e., spontaneous recurrent seizures) has not been tested. In the present study, long-term seizure monitoring and histology was used to test for temporal lobe epilepsy following prenatal exposure to DA. In Experiment One, the previous study's in utero DA treatment protocol was replicated, including use of the CD-1 mouse strain. Afterward, mice were video-monitored for convulsive seizures from 2 to 6 months old. None of the CD-1 mice treated in utero with vehicle or DA was observed to experience spontaneous convulsive seizures. After seizure monitoring, mice were evaluated for pathological evidence of temporal lobe epilepsy. None of the mice treated in utero with DA displayed the hilar neuron loss that occurs in patients with temporal lobe epilepsy and in the mouse pilocarpine model of temporal lobe epilepsy. In Experiment Two, a higher dose of DA was administered to pregnant FVB mice. FVB mice were tested as a potentially more sensitive strain, because they have a lower seizure threshold, and some females spontaneously develop epilepsy. Female offspring were monitored with continuous video and telemetric bilateral hippocampal local field potential recording at 1-11 months old. A similar proportion of vehicle- and DA-treated female FVB mice spontaneously developed epilepsy, beginning in the fourth month of life. Average seizure frequency and duration were similar in both groups. Seizure frequency was lower than that of positive-control pilocarpine-treated mice, but seizure duration was similar. None of the mice treated in utero with vehicle or DA displayed hilar neuron loss or intense mossy fiber sprouting, a form of aberrant synaptic reorganization that develops in patients with temporal lobe epilepsy and in pilocarpine-treated mice. FVB mice that developed epilepsy (vehicle- and DA-treated) displayed mild mossy fiber sprouting. Results of this study suggest that a single subconvulsive dose of DA at mid-gestation does not cause temporal lobe epilepsy in mice.

中文翻译：

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妊娠中期单次惊厥剂量的海藻酸不会引起小鼠颞叶癫痫。

产生海藻酸（DA）的藻类的有害繁殖是全世界海洋中的一个问题。DA是一种有效的谷氨酸受体激动剂，可引起癫痫持续状态，并在幸存者中引起颞叶癫痫。在小鼠中，据报道，一次在子宫内低剂量暴露于DA会引起海马损伤和癫痫样活动，导致这一假说，即孕妇未受污染的海鲜暴露于DA导致无法识别的暴露会损害胎儿海马并启动颞叶癫痫发生。但是，癫痫的发展（即自发性反复发作）尚未得到测试。在本研究中，长期癫痫发作监测和组织学被用于测试产前暴露于DA后的颞叶癫痫。在实验一中，复制了先前研究的子宫内DA治疗方案，包括使用CD-1小鼠品系。然后，对小鼠进行2个月至6个月大的惊厥性癫痫发作视频监控。在子宫中用媒介物或DA处理的CD-1小鼠均未观察到自发性惊厥性癫痫发作。监测癫痫发作后，评估小鼠颞叶癫痫的病理学证据。在子宫内用DA治疗的小鼠均未显示在颞叶癫痫患者和颞叶癫痫的小鼠毛状芸香模型中发生的肺门神经元丢失。在实验二中，对怀孕的FVB小鼠给予了更高剂量的DA。FVB小鼠被测试为可能更敏感的品系，因为它们的癫痫发作阈值较低，并且某些雌性动物自发发展为癫痫病。在1-11个月大时，通过连续视频和遥测双侧海马局部场电位监测雌性后代。从出生后第四个月开始，接受媒介物和DA治疗的雌性FVB小鼠自发发生癫痫病的比例相似。两组的平均癫痫发作频率和持续时间相似。癫痫发作频率低于阳性对照毛果芸香碱治疗的小鼠，但癫痫发作持续时间相似。在子宫内用媒介物或DA治疗的小鼠均未显示肺门神经元丢失或苔藓纤维强烈萌发，这是颞叶癫痫患者和经毛果芸香碱治疗的小鼠中异常突触重组的一种形式。发生癫痫的FVB小鼠（经车辆和DA处理）显示出轻度的苔藓纤维发芽。