Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain
Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain
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DOI：
10.1016/j.ijdevneu.2005.07.005
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发表时间：
2005-11-01
影响因子：
1.8
通讯作者：
Zharkovsky, A
中科院分区：
文献类型：
--
作者：
Jaako-Movits, K;Zharkovsky, T;Zharkovsky, A
研究了发育期铅暴露对 60-80 天大大鼠的情绪反应、情境恐惧调节和齿状回神经发生的影响。从出生后第 1 天到 PND 21，Wistar 幼鼠通过其母亲的饮用水暴露于 0.2% 醋酸铅，并从断奶到 PND 30 直接通过饮用水暴露于 0.2% 醋酸铅。在 PND 60 和 80 时，分别研究了焦虑和情境恐惧条件反射的水平。在 PND 80 时，所有动物均接受 BrdU 注射，以确定 Pb 对海马齿状回新细胞生成及其存活和分化模式的影响。本研究的结果表明，发育期铅暴露会导致焦虑水平持续增加，并抑制情境恐惧调节。发育过程中的铅暴露减少了齿状回新细胞的生成，并改变了 BrdU 阳性细胞分化为成熟神经元的模式。 BrdU 阳性细胞与成熟神经元标记物钙结合蛋白共表达的比例较低。相比之下，在铅暴露的动物中，未完全分化的年轻神经元的比例和新生细胞产生的星形胶质细胞的比例增加。我们的结果表明，发育期铅暴露会诱导神经发生的持续抑制，并改变大鼠海马齿状回新生细胞的分化模式，这可能至少部分导致行为和认知障碍 成年后观察到。 (c) 2005 年 ISDN。由爱思唯尔有限公司出版。保留所有权利。
The effects of developmental lead exposure on the emotional reactivity, contextual fear conditioning and neurogenesis in the dentate gyrus of 60-80 days-old rats were studied. Wistar rat pups were exposed to 0.2% lead acetate via their dams' drinking water from postnatal day (PND) 1 to PND 21 and directly via drinking water from weaning until PND 30. At PND 60 and 80 the level of anxiety and contextual fear conditioning were studied, respectively. At PND 80 all animals received injections of BrdU to determine the effects of Pb on the generation of new cells in the dentate gyrus of hippocampus and on their survival and differentiation patterns. The results of the present study demonstrate that developmental lead exposure induces persistent increase in the level of anxiety and inhibition of contextual fear conditioning. Developmental lead exposure reduced generation of new cells in the dentate gyrus and altered the pattern of differentiation of BrdU-positive cells into mature neurons. A lower proportion of BrdU-positive cells co-expressed with the marker for mature neurons, calbindin. In contrast, the proportions of young not fully differentiated neurons and proportions of astroglial cells, generated from newly born cells, were increased in lead-exposed animals.Our results demonstrate that developmental lead exposure induces persistent inhibition of neurogenesis and alters the pattern of differentiation of newly born cells in the dentate gyrus of rat hippocampus, which could, at least partly, contribute to behavioral and cognitive impairments observed in adulthood. (c) 2005 ISDN. Published by Elsevier Ltd. All rights reserved.