Developmental time course and effects of immunostressors that alter hormone-responsive behavior on microglia in the peripubertal and adult female mouse brain.
Developmental time course and effects of immunostressors that alter hormone-responsive behavior on microglia in the peripubertal and adult female mouse brain.
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DOI：
10.1371/journal.pone.0171381
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Blaustein JD
中科院分区：
文献类型：
--
作者：
Holder MK;Blaustein JD
在雌性小鼠中，在青春期发育期间被从繁殖设施运送或注射细菌内毒素脂多糖（LPS）的经历改变了成年后对雌二醇的行为反应，这可以通过雌二醇对性行为、认知功能以及其抗焦虑和抗抑郁特性的干扰来证明。小胶质细胞是大脑中主要的免疫细胞类型，对大脑发育和应激反应有显著而持久的形态和功能变化。在这里，我们描述了小胶质细胞的形态和它们对运输和LPS的反应在青春期和成年雌性小鼠。与没有免疫刺激的成年小鼠相比，处于青春期前后的小鼠在海马、杏仁核和下丘脑中有更多具有长而厚突起的小胶质细胞。免疫刺激也增加了离子钙结合接头分子1 （Iba1）的免疫反应性（IR）， Iba1在小胶质细胞中组成性表达。在海马体中，动物的年龄对从繁殖设施运输或LPS暴露后Iba1- IR的增加没有影响。在杏仁核中，我们观察到与成年小鼠相比，在装运或LPS处理后，青春期周围小鼠的Iba1-IR更多。在下丘脑，运输和LPS处理的影响是分离的，因为LPS处理，而不是运输，诱导了Iba1-IR的增加。综上所述，这些数据表明，青春期小鼠和成年小鼠的小胶质细胞形态存在差异；此外，与成年小鼠相比，青春期小鼠的小胶质细胞对复杂应激源的反应更大。
In female mice, the experience of being shipped from the breeder facility or a single injection of the bacterial endotoxin, lipopolysaccharide (LPS), during pubertal development alters the behavioral response to estradiol in adulthood as demonstrated by perturbations of estradiol’s effects on sexual behavior, cognitive function, as well as its anxiolytic and anti-depressive properties. Microglia, the primary type of immunocompetent cell within the brain, contribute to brain development and respond to stressors with marked and long-lasting morphological and functional changes. Here, we describe the morphology of microglia and their response to shipping and LPS in peripubertal and adult female mice. Peripubertal mice have more microglia with long, thick processes in the hippocampus, amygdala and hypothalamus as compared with adult mice in the absence of an immune challenge. An immune challenge also increases immunoreactivity (IR) of ionized calcium binding adaptor molecule 1 (Iba1), which is constitutively expressed in microglia. In the hippocampus, the age of animal was without effect on the increase in Iba1- IR following shipping from the breeder facility or LPS exposure. In the amygdala, we observed more Iba1-IR following shipping or LPS treatment in peripubertal mice, compared to adult mice. In the hypothalamus, there was a disassociation of the effects of shipping and LPS treatment as LPS treatment, but not shipping, induced an increase in Iba1-IR. Taken together these data indicate that microglial morphologies differ between pubertal and adult mice; moreover, the microglial response to complex stressors is greater in pubertal mice as compared to adult mice.