Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood
Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood
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DOI：
10.1016/j.bbi.2006.10.005
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发表时间：
2007-03-01
影响因子：
15.1
通讯作者：
Maier, Steven F.
中科院分区：
文献类型：
--
作者：
Bilbo, Staci D.;Newsum, Nicholas J.;Maier, Steven F.
我们之前已经证明，新生大鼠的细菌感染（大肠杆菌）与成年期恐惧调节任务中的记忆受损有关。然而，只有在学习期间进行外周免疫激发（脂多糖；LPS）时才会观察到这种损害。我们使用了一个简短的分离/处理范例来确定是否可以预防与新生儿感染相关的成人记忆障碍。孕产妇护理中自然发生的变化会促进后代认知发展的显着变化，并且处理范式用于操纵孕产妇护理的质量和数量。大鼠在产后 (P) 第 4 天注射大肠杆菌或 PBS，从 P4 到 20，每组的一半大鼠每天接受 15 分钟的处理。然后所有大鼠在成年后进行测试。对新生儿时感染的大鼠进行处理可防止海马内小胶质细胞标记物反应性的增加，以及感染通常产生的 LPS 的大脑 IL-1 β 的过度产生。因此，这些神经过程现在与未感染的 PBS 对照的水平相当。此外，在新生儿感染的成年大鼠的环境恐惧任务中，处理完全防止了脂多糖引起的记忆障碍。最后，新生儿处理显着改善了早期接受 PBS 治疗的大鼠的空间学习和记忆并减少了焦虑，但对新生儿感染的大鼠的这些措施没有有益影响。总而言之，这些数据表明，产妇护理可能会对成年期的神经炎症过程产生深远的影响，并且感染也可能会阻止产妇护理对以后生活认知的影响。 (c) 2006 Elsevier Inc. 保留所有权利。
We have previously demonstrated that bacterial infection (Escherichia coli) in neonatal rats is associated with impaired memory in a fear-conditioning task in adulthood. This impairment, however, is only observed if a peripheral immune challenge (lipopolysaccharide; LPS) is administered around the time of learning. We used a brief separation/handling paradigm to determine if the adult memory impairment associated with neonatal-infection could be prevented. Naturally occurring variations in maternal care promote striking variations in offspring cognitive development, and handling paradigms are used to manipulate the quality and quantity of maternal care. Rats were injected on post-natal (P) day 4 with E coli or PBS, and half from each group were handled for 15 min/day from P4 to 20. All rats were then tested in adulthood. Neonatal handling of rats infected as neonates prevented the increase in microglial cell marker reactivity within the hippocampus, and the exaggerated brain IL-1 beta production to LPS normally produced by the infection. Thus, these neural processes were now comparable to levels of non-infected PBS controls. Furthermore, handling completely prevented LPS-induced memory impairment in a context-fear task in adult rats infected as neonates. Finally, neonatal handling dramatically improved spatial learning and memory and decreased anxiety in rats treated early with PBS, but had no beneficial effect on these measures in rats infected as neonates. Taken together, these data suggest that maternal care may profoundly influence neuroinflammatory processes, in adulthood, and that infection may also prevent maternal care influences on cognition later in life. (c) 2006 Elsevier Inc. All rights reserved.