Prenatal alcohol-induced sex differences in immune, metabolic and neurobehavioral outcomes in adult rats.
Prenatal alcohol-induced sex differences in immune, metabolic and neurobehavioral outcomes in adult rats.
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DOI：
10.1016/j.bbi.2021.08.207
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Sohrabji F
中科院分区：
文献类型：
--
作者：
Bake S;Pinson MR;Pandey S;Chambers JP;Mota R;Fairchild AE;Miranda RC;Sohrabji F
产前酒精暴露（PAE）可导致神经行为异常，这种异常可能因代谢和免疫系统缺陷共同发生而加剧。为了验证成年PAE后代的外周炎症与葡萄糖代谢不良和神经认知缺陷有关的假设，怀孕的Sprague-Dawley大鼠在妊娠后半期暴露于乙醇蒸气或环境空气中。我们通过流式细胞术评估了成年雄性和雌性后代在一系列神经认知行为、葡萄糖耐量、循环和脾脏免疫细胞以及循环和组织（肝脏、肠系膜脂肪和脾脏）细胞因子方面的表现。PAE降低脾脏重量比和脾脏调节性t细胞（Treg）数量。PAE的男性，而不是女性表现出循环单核细胞的增加。总体而言，PAE雄性小鼠表现出细胞因子水平的抑制，而PAE雌性小鼠表现出肠系膜脂肪组织（IL-6和il -1 α）和肝脏（IFN-γ、IL-1β、IL-13、IL-18、IL-12p70和MCP-1）细胞因子水平的升高，并伴有葡萄糖耐受不良的增加。行为分析也显示了PAE效应的性别依赖性。pae -男性表现出增加的焦虑样行为，而pae -女性表现出减少的社会互动。两种性别的PAE后代都表现出对新物体的识别能力受损。多线性回归模型预测外周免疫状态、葡萄糖耐受不良和行为结果之间的关系，结果显示，在PAE后代中，较高水平的脂肪瘦素和肝脏TNF- α预测较高的循环葡萄糖水平。较低的肝脏IL-1 α和较高的血浆fractalkine预示着在空地中心停留的时间更长，而性别是另一个预测因素。较高的循环和脾treg预示着pae后代更好的社会互动。总的来说，我们的数据表明，外周免疫状态是成年PAE后代葡萄糖耐受不良和神经行为功能的持久、性别依赖的预测因子。
Prenatal alcohol exposure (PAE) can result in neurobehavioral anomalies, that may be exacerbated by co-occurring metabolic and immune system deficits. To test the hypothesis that the peripheral inflammation in adult PAE offspring is linked to poor glucose metabolism and neurocognitive deficits, pregnant Sprague-Dawley rats were exposed to ethanol vapor or ambient air during the latter half of gestation. We assessed, in adult offspring of both sexes, performance on a battery of neurocognitive behaviors, glucose tolerance, circulating and splenic immune cells by flow-cytometry, and circulating and tissue (liver, mesenteric adipose, and spleen) cytokines by multiplexed assays. PAE reduced both the ratio of spleen to body weight and splenic regulatory T-cell (Treg) numbers. PAE males, but not females exhibited an increase in circulating monocytes. Overall, PAE males exhibited a suppression of cytokine levels, while PAE females exhibited elevated cytokines in mesenteric adipose tissue (IL-6 and IL1α) and liver (IFN-γ, IL-1β, IL-13, IL-18, IL-12p70, and MCP-1), along with increased glucose intolerance. Behavioral analysis also showed sex-dependent PAE effects. PAE-males exhibited increased anxiety-like behavior while PAE-females showed decreased social interaction. PAE offspring of both sexes exhibited impaired recognition of novel objects. Multilinear regression modeling to predict the association between peripheral immune status, glucose intolerance and behavioral outcomes, showed that in PAE offspring, higher levels of adipose leptin and liver TNF- α predicted higher circulating glucose levels. Lower liver IL-1 α and higher plasma fractalkine predicted more time spent in the center of an open-field with sex being an additional predictor. Higher circulating and splenic Tregs predicted better social interaction in the PAE-offspring. Collectively, our data show that peripheral immune status is a persistent, sex-dependent predictor of glucose intolerance and neurobehavioral function in adult PAE offspring.
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DOI：
10.1038/ijo.2015.52
发表时间：
2015-08
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Darkhal P;Gao M;Ma Y;Liu D
通讯作者：
Liu D
DOI：
10.1038/s41577-019-0131-x
发表时间：
2019-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Altan-Bonnet G;Mukherjee R
通讯作者：
Mukherjee R
DOI：
10.1111/acer.13277
发表时间：
2017-01
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bake S;Gardner R;Tingling JD;Miranda RC;Sohrabji F
通讯作者：
Sohrabji F
影响因子：
5.3
作者：
Brachman, Rebecca A.;Lehmann, Michael L.;Herkenham, Miles
通讯作者：
Herkenham, Miles
影响因子：
9.3
作者：
Bodnar, Tamara S.;Raineki, Charlis;Weinberg, Joanne
通讯作者：
Weinberg, Joanne