Coyle Peter, Tran Nancy, Fung Jenny N T, Summers Brooke L, Rofe Allan M
Division of Clinical Biochemistry, Hanson Institute and Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia.
Behav Brain Res. 2009 Jan 30;197(1):210-8. doi: 10.1016/j.bbr.2008.08.022. Epub 2008 Aug 28.
Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental damage. While the mechanism is unclear accumulating evidence suggests that the maternal inflammatory response may be responsible. Metallothionein (MT) is a zinc (Zn)-binding protein that when induced in the mother's liver during the acute phase response has been found to cause a fetal Zn deficiency. Infection-mediated fetal Zn deficiency in early pregnancy has been shown to cause teratogenicity which can be prevented by dietary Zn supplementation throughout pregnancy. This study examined whether cognitive impairments can be caused by lipopolysaccharide (LPS) administration early in pregnancy and whether dietary Zn supplementation can ameliorate these changes. Maternal inflammation induced by LPS at gestation day (GD) 8 did not affect spatial learning or memory of adult mice offspring in a water cross-maze escape task. However, in an object recognition task, where control mice demonstrated good visual recognition memory by exploring a novel object more than a familiar object, LPS-treated offspring demonstrated abnormal perseverant exploration towards the familiar object that cannot be explained in full by impaired object recognition memory. In comparison, offspring of mice from dams given LPS and dietary Zn supplementation displayed normal object recognition task performance. Microarray analysis on the brain of GD 12 fetuses did not identify any differentially expressed genes between treatment groups. This study demonstrates that LPS administration in early pregnancy can cause an anomaly in object recognition that can be measured in adult offspring. This aberrant behaviour can be prevented by dietary Zn supplementation during pregnancy, thus providing a nutritional strategy to limit neurodevelopmental damage caused by infections early in pregnancy.
孕期母体感染与神经发育损伤风险增加有关。虽然其机制尚不清楚，但越来越多的证据表明，母体炎症反应可能是原因所在。金属硫蛋白（MT）是一种锌（Zn）结合蛋白，在急性期反应期间，当它在母亲肝脏中被诱导产生时，已被发现会导致胎儿锌缺乏。已表明，妊娠早期感染介导的胎儿锌缺乏会导致致畸性，而在整个孕期补充膳食锌可预防这种情况。本研究调查了孕期早期给予脂多糖（LPS）是否会导致认知障碍，以及膳食锌补充是否能改善这些变化。在妊娠第8天（GD8）由LPS诱导的母体炎症，在水迷宫逃避任务中并未影响成年小鼠后代的空间学习或记忆。然而，在物体识别任务中，对照小鼠通过对新物体的探索多于熟悉物体来表现出良好的视觉识别记忆，而接受LPS处理的后代对熟悉物体表现出异常的持续探索，这不能完全用物体识别记忆受损来解释。相比之下，给予LPS并补充膳食锌的母鼠所产后代在物体识别任务中表现正常。对GD12胎儿大脑进行的微阵列分析未发现各治疗组之间有任何差异表达基因。本研究表明，孕期早期给予LPS可导致成年后代出现可测量的物体识别异常。孕期补充膳食锌可预防这种异常行为，从而提供一种营养策略来限制孕期早期感染所致的神经发育损伤。
