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三甲基锡(TMT)诱导大鼠脑损伤的行为、生化及组织学效应

Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat.

作者信息

Earley B, Burke M, Leonard B E

机构信息

Pharmacology Department, University College, Galway, Ireland.

出版信息

Neurochem Int. 1992 Oct;21(3):351-66. doi: 10.1016/0197-0186(92)90186-u.

Abstract

To assess the nature and extent of behavioural, biochemical and histological changes induced by trimethyltin (TMT), rats were treated with a single injection of TMT over a dose range of 6, 7 and 8 mg/kg i.p. Behavioural observations were performed at a minimum of 21 days after the administration of TMT. The behavioural consequences of TMT were hyperactivity in the open-field test, increased locomotor activity and deficits in passive and active avoidance behaviour, T-maze alternation and Morris Water Maze behaviour. The behavioural changes were dose dependent and were accompanied by a degree of pathological damage to the hippocampal pyramidal cells which was particularly apparent at the highest dose. The main biochemical effects of TMT involved deficits in the serotonergic and GABA-ergic systems and a decrease in M1 and M2 binding sites in the hippocampus. These results suggest that the toxic interaction of TMT with the hippocampus and other limbic brain regions may be responsible for its effect on learning and memory.

摘要

为评估三甲基锡(TMT)诱导的行为、生化和组织学变化的性质及程度,给大鼠腹腔注射6、7和8mg/kg剂量范围的TMT进行单次处理。在给予TMT后至少21天进行行为观察。TMT的行为后果包括旷场试验中的多动、运动活动增加以及被动和主动回避行为、T迷宫交替和莫里斯水迷宫行为缺陷。行为变化呈剂量依赖性,并伴有海马锥体细胞一定程度的病理损伤,这在最高剂量时尤为明显。TMT的主要生化作用涉及血清素能和γ-氨基丁酸能系统缺陷以及海马中M1和M2结合位点减少。这些结果表明,TMT与海马及其他边缘脑区的毒性相互作用可能是其对学习和记忆产生影响的原因。

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