Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood.
Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood.
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DOI：
10.1186/s12974-014-0155-x
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发表时间：
2014-09-17
影响因子：
9.3
通讯作者：
Layé S
中科院分区：
文献类型：
--
作者：
Dinel AL;Joffre C;Trifilieff P;Aubert A;Foury A;Le Ruyet P;Layé S
出生后时期是一个关键的时间窗口，在此期间，炎症事件对大脑产生显著和持久的影响，因此，在以后的生活中诱导情感行为和/或认知的改变。然而，新生儿炎症对青春期行为的长期影响，这是神经发育性精神障碍发展的敏感时期，却很少有人研究。在这项研究中，我们研究了早期炎症挑战是否会改变青春期和成年期的情绪行为和空间记忆，以及压力轴活动、炎症反应和神经发生是否受到影响。在出生后第14天（PND）对小鼠施用脂多糖（LPS，100 μg/kg），并在3小时后测量血浆和脑结构中的细胞因子表达。在青春期（PND 30）和成年期（PND 90）测量了痴呆样和抑郁样行为（分别在新奇抑制喂养试验和强迫游泳试验中测量）和空间记忆（Y-迷宫试验）。在成年时测量下丘脑-垂体-肾上腺（HPA）轴活动（海马和前额叶皮质中的血浆皮质酮和糖皮质激素受体）。此外，测量了新的成人LPS攻击（100 μ g/kg）对空间记忆（Y-迷宫测试）、神经发生（海马中的双皮质素阳性细胞数）和血浆细胞因子表达的影响。首先，我们表明，在PND 14的幼崽，LPS的外周给药诱导的血浆和脑结构中的促炎和抗炎细胞因子的表达，研究3小时后给药。青春期小鼠的抑郁样行为发生了改变，但成年小鼠没有，而抑郁样行为在青春期没有发生，在成年期增加。这伴随着前额叶皮质糖皮质激素受体磷酸化的降低，对皮质酮水平没有影响。第二，新生儿LPS治疗对青春期和成年期的空间记忆没有影响。然而，成年期LPS的第二次挑战损害了空间记忆能力和神经发生，并增加了循环中的CCL 2水平。我们的研究首次表明，在小鼠中，在PND 14的外周LPS治疗差异性地改变了青春期和成年期的情绪行为，但不改变空间记忆。PND 14的行为学效应可能与HPA轴失调和神经发生障碍有关。
The postnatal period is a critical time window during which inflammatory events have significant and enduring effects on the brain, and as a consequence, induce alterations of emotional behavior and/or cognition later in life. However, the long-term effect of neonatal inflammation on behavior during adolescence, a sensitive period for the development of neurodevelopmental psychiatric disorders, has been little studied. In this study, we examined whether an early-life inflammatory challenge could alter emotional behaviors and spatial memory at adolescence and adulthood and whether stress axis activity, inflammatory response and neurogenesis were affected. Lipopolysaccharide (LPS, 100 μg/kg) was administered to mice on postnatal day (PND) 14 and cytokine expression was measured in the plasma and in brain structures 3 hours later. Anxiety-like and depressive-like behavior (measured in the novelty-suppressed feeding test and the forced swim test, respectively) and spatial memory (Y-maze test) were measured at adolescence (PND30) and adulthood (PND90). Hypothalamic-pituitary-adrenal (HPA) axis activity (plasma corticosterone and glucocorticoid receptors in the hippocampus and prefrontal cortex) was measured at adulthood. In addition, the impact of a novel adult LPS challenge (100 μ/kg) was measured on spatial memory (Y-maze test), neurogenesis (doublecortin-positive cell numbers in the hippocampus) and plasma cytokine expression. First, we show in PND14 pups that a peripheral administration of LPS induced the expression of pro- and anti-inflammatory cytokines in the plasma and brain structures that were studied 3 hours after administration. Anxiety-like behavior was altered in adolescent, but not in adult, mice, whereas depressive-like behavior was spared at adolescence and increased at adulthood. This was accompanied by a decreased phosphorylation of the glucocorticoid receptor in the prefrontal cortex, with no effect on corticosterone levels. Second, neonatal LPS treatment had no effect on spatial memory in adolescence and adulthood. However, a second challenge of LPS in adulthood impaired spatial memory performance and neurogenesis and increased circulating levels of CCL2. Our study shows for the first time, in mice, that a peripheral LPS treatment at PND14 differentially alters emotional behaviors, but not spatial memory, at adolescence and adulthood. The behavioral effect of LPS at PND14 could be attributed to HPA axis deregulation and neurogenesis impairment.
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影响因子：
3.7
作者：
Foley KA;Ossenkopp KP;Kavaliers M;Macfabe DF
通讯作者：
Macfabe DF
影响因子：
11
作者：
Anacker, C.;Zunszain, P. A.;Cattaneo, A.;Carvalho, L. A.;Garabedian, M. J.;Thuret, S.;Price, J.;Pariante, C. M.
通讯作者：
Pariante, C. M.
影响因子：
2.7
作者：
Bilbo, SD;Rudy, JW;Maier, SF
通讯作者：
Maier, SF
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
5.3
作者：
Bilbo, SD;Biedenkapp, JC;Maier, SF
通讯作者：
Maier, SF