Wang Jun, Cao Bing, Yang Xiangwei, Wu Jiajun, Chan Leo Lai, Li Ying
Department of Biomedical Sciences , City University of Hong Kong , Hong Kong , P.R. China . Email:
Centre for Biosystems , Neuroscience , and Nanotechnology , City University of Hong Kong , Hong Kong , P.R. China.
Toxicol Res (Camb). 2016 Jun 8;6(2):179-187. doi: 10.1039/c5tx00475f. eCollection 2017 Mar 1.
Ciguatoxins are marine biotoxins that induce the human poisoning syndrome known as ciguatera fish poisoning (CFP). In humans, different kinds of neurological symptoms have been reported after CFP, including anxiety, depression and memory loss. Repetitive exposures to sub-threshold levels of ciguatera toxins may cause irreversible sub-clinical damage, and eventually cause more severe illness. Our previous study has shown that an acute single dose of Pacific ciguatoxin-1 (P-CTX-1) induced synaptic facilitation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus-anterior cingulate cortex pathway. Reactive astrogliosis was detected in acute ciguatera poisoning. Despite the reports of complex and prolonged neurological symptoms in patients, few studies have been conducted in animal models to investigate the emotional and cognitive deficits after chronic exposure to ciguatoxin. In the present study, using a rat model with repeated exposures to low dosage of P-CTX-1, we observed development of anxiety-like behavior by open field test and elevated plus maze test, and learning and memory deficits by the Morris water maze; further, decision-making impairment was determined in the chronic P-CTX-1-treated rats by the rats gambling task. We conclude that chronic ciguatera poisoning leads to anxiety, and to impairment of spatial reference memory and decision-making behavior.
雪卡毒素是一种海洋生物毒素,可引发被称为雪卡鱼中毒(CFP)的人体中毒综合征。在人类中,雪卡鱼中毒后会出现不同类型的神经症状,包括焦虑、抑郁和失忆。反复接触低于阈值水平的雪卡毒素可能会导致不可逆的亚临床损伤,并最终引发更严重的疾病。我们之前的研究表明,急性单次剂量的太平洋雪卡毒素-1(P-CTX-1)会诱导内侧丘脑-前扣带回皮质通路中的突触易化,并阻断电刺激诱导的长时程增强的诱导。在急性雪卡鱼中毒中检测到了反应性星形胶质细胞增生。尽管有报道称患者会出现复杂且持续时间长的神经症状,但在动物模型中针对慢性接触雪卡毒素后的情绪和认知缺陷进行的研究却很少。在本研究中,我们使用反复接触低剂量P-CTX-1的大鼠模型,通过旷场试验和高架十字迷宫试验观察到了焦虑样行为的发展,通过莫里斯水迷宫观察到了学习和记忆缺陷;此外,通过大鼠赌博任务确定了慢性P-CTX-1处理的大鼠存在决策障碍。我们得出结论,慢性雪卡鱼中毒会导致焦虑,以及空间参考记忆和决策行为受损。