Evidence for an immune signature of prenatal alcohol exposure in female rats
Evidence for an immune signature of prenatal alcohol exposure in female rats
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DOI：
10.1016/j.bbi.2016.05.022
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发表时间：
2016-11-01
影响因子：
15.1
通讯作者：
Weinberg, Joanne
中科院分区：
文献类型：
--
作者：
Bodnar, Tamara S.;Hill, Lesley A.;Weinberg, Joanne
越来越多的证据表明，免疫/神经免疫紊乱可能是包括神经发育障碍在内的一系列疾病的根本原因。尽管产前酒精暴露（PAE）会影响免疫功能，但迄今为止很少有研究调查PAE后免疫功能与长期负面健康结果的关系，而且大多数研究都集中在男性身上。为了填补这一空白，我们利用大鼠模型来研究PAE对PAE和对照雌性小鼠在生命早期[出生后第1天（P1）， P8和P22]免疫/神经免疫功能的影响。由于免疫系统和内分泌系统之间存在广泛的相互作用，我们还测量了皮质酮和皮质酮结合球蛋白（CBG）的水平。虽然各组间皮质酮水平没有差异，但P1至P8 PAE后代的CBG水平较低，表明皮质酮储存量较低，可能是炎症易感性的基础。P22是免疫功能改变的标志，PAE大鼠脾脏重量增加。此外，与P8上的对照组相比，我们在PAE中检测到一种独特的细胞因子谱——PFC和海马的水平较高，下丘脑和脾脏的水平较低。在胎儿酒精谱系障碍（FASD）儿童的敏感发育时期发现PAE后代的特异性免疫特征，这对于理解胎儿酒精谱系障碍（FASD）儿童长期免疫改变的基础和健康结局具有重要意义。我们的研究结果还强调了未来基于免疫的干预策略可以被视为FASD个体的辅助新治疗方法的可能性。(C) 2016 Elsevier Inc.版权所有。
Evidence for immune/neuroimmune disturbances as a possible root cause of a range of disorders, including neurodevelopmental disorders, is growing. Although prenatal alcohol exposure (PAE) impacts immune function, few studies to date have examined immune function in relation to long-term negative health outcomes following PAE, and most have focused on males. To fill this gap, we utilized a rat model to examine the effects of PAE on immune/neuroimmune function during early-life [postnatal day 1 (P1), P8, and P22] in PAE and control females. Due to the extensive interplay between the immune and endocrine systems, we also measured levels of corticosterone and corticosterone binding globulin (CBG). While corticosterone levels were not different among groups, CBG levels were lower in PAE offspring from P1 to P8, suggesting a lower corticosterone reservoir that may underlie susceptibility to inflammation. Spleen weights were increased in PAE rats on P22, a marker of altered immune function. Moreover, we detected a unique cytokine profile in PAE compared to control offspring on P8 - higher levels in the PFC and hippocampus, and lower levels in the hypothalamus and spleen. The finding of a specific immune signature in PAE offspring during a sensitive developmental period has important implications for understanding the basis of long-term immune alterations and health outcomes in children with Fetal Alcohol Spectrum Disorder (FASD). Our findings also highlight the future possibility that immune-based intervention strategies could be considered as an adjunctive novel therapeutic approach for individuals with FASD. (C) 2016 Elsevier Inc. All rights reserved.