Filliat Pierre, Coubard Stéphanie, Pierard Christophe, Liscia Pierrette, Beracochea Daniel, Four Elise, Baubichon Dominique, Masqueliez Catherine, Lallement Guy, Collombet Jean-Marc
Département de Toxicologie, Centre de Recherches du Service de Santé des Armées Emile Pardé, 24 Avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche Cedex, France.
Neurotoxicology. 2007 May;28(3):508-19. doi: 10.1016/j.neuro.2006.11.004. Epub 2006 Nov 18.
We investigated the long-term (up to 90 days) consequences of soman intoxication in mice on weight, motor performances (grip strength, rotarod) and mnemonic cognitive processes (T-maze, Morris water maze test). First, a relative weight loss of 20%, measured 3 days after intoxication, was evidenced as a threshold beyond which neuropathological damage was observed in the hippocampus. Animals were then distributed into either low weight loss (LWL) or high weight loss (HWL) groups according to the relative 20% weight loss threshold. Compared to controls, both groups of poisoned mice quickly exhibited a decrease in their motor performance subsequent to an acute soman toxicity phase. Then, total motor recovery occurred for the LWL group. Comparatively, HWL mice showed only transient recovery prior to a second decrease phase due to soman-induced delayed toxicity. One month after intoxication, mnemonic cognitive performances of the LWL group were similar to controls while the HWL group did not exhibit any learning skill. Three months after poisoning, compared to controls, the LWL group showed similar mnemonic performances in the maze test but a mild deficit in the Morris water maze task. At the same time, learning skills slightly recovered in the HWL group. Mnemonic cognitive data are discussed in relation to the neuropathology, neurogenesis and sprouting occurring in the hippocampus of soman-intoxicated animals.
我们研究了小鼠梭曼中毒的长期(长达90天)后果,包括体重、运动能力(握力、转棒试验)和记忆认知过程(T迷宫、莫里斯水迷宫试验)。首先,中毒后3天测得的20%相对体重减轻被证明是一个阈值,超过该阈值时,在海马体中观察到神经病理学损伤。然后,根据20%相对体重减轻阈值,将动物分为低体重减轻(LWL)组或高体重减轻(HWL)组。与对照组相比,两组中毒小鼠在急性梭曼毒性期后均迅速出现运动能力下降。然后,LWL组实现了完全运动恢复。相比之下,HWL组小鼠在因梭曼诱导的延迟毒性导致的第二个下降阶段之前仅表现出短暂恢复。中毒后一个月,LWL组的记忆认知表现与对照组相似,而HWL组未表现出任何学习技能。中毒三个月后,与对照组相比,LWL组在迷宫试验中的记忆表现相似,但在莫里斯水迷宫任务中存在轻度缺陷。与此同时,HWL组的学习技能略有恢复。结合梭曼中毒动物海马体中发生的神经病理学、神经发生和发芽情况,对记忆认知数据进行了讨论。