Sex-Dependent Effects of Neonatal Inflammation on Adult Inflammatory Markers and Behavior
Sex-Dependent Effects of Neonatal Inflammation on Adult Inflammatory Markers and Behavior
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DOI：
10.1210/en.2009-1101
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Pittman, Q. J.
中科院分区：
文献类型：
--
作者：
Kentner, A. C.;McLeod, S. A.;Pittman, Q. J.
炎症分子，如环氧合酶（考克斯），一种前列腺素合成酶，已被确定为抑郁症的标志物。以前，我们已经观察到升高的基础考克斯-2表达在成年雄性大鼠的下丘脑经腹腔注射脂多糖（LPS），这可能表明一个表型破坏享乐行为，抑郁症的症状。然而，考克斯-2及其对快感缺失行为表达的贡献尚未在这些雄性或雌性大鼠的整个发情周期中进行研究，这是当前工作的目的。在这里，我们研究的影响，新生儿LPS的挑战或生理盐水的蔗糖偏好测试作为衡量快感缺乏症，下丘脑考克斯-2的表达，在成年雄性和自由骑自行车的雌性大鼠。我们的数据表明，在出生后第14天的新生儿LPS引起升高的基础表达的下丘脑考克斯-2在男性，但不是在女性，大鼠的性别差异。此外，雄性和雌性大鼠的基线蔗糖偏好作为新生儿LPS治疗或发情周期阶段的函数没有改变。在雄性和雌性动物中，50 μ g/kg LPS在成年期引起血浆IL-6和下丘脑考克斯-2表达升高，但在腹腔注射LPS治疗的大鼠中，这种表达显著降低;这种新生儿编程对于蔗糖偏好或总液体摄入量（即使在高剂量LPS后）也不明显。我们的数据表明，炎症和快感缺失行为之间的分离和新生儿炎症在男性和女性的差异影响。（内分泌学151：2689-2699，2010）
Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 mu g/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females. (Endocrinology 151: 2689-2699, 2010)