Differential effects of homotypic vs. heterotypic chronic stress regimens on microglial activation in the prefrontal cortex.

Differential effects of homotypic vs. heterotypic chronic stress regimens on microglial activation in the prefrontal cortex.
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DOI:
10.1016/j.physbeh.2013.05.030
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发表时间:
2013-10-02
影响因子:
2.9
通讯作者:
Herman JP
Herman JP
中科院分区:
医学3区
文献类型:
--
作者:
Kopp BL;Wick D;Herman JP

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应激病理与下丘脑-垂体-肾上腺(HPA)轴失调和异常的糖皮质激素反应有关。最近的研究表明,在反复抑制后,前额皮质离子钙结合适配体分子1 (Iba-1)染色增加,反映了小胶质细胞密度的增加。我们的实验检测了Iba-1染色在重复约束(RR)和慢性可变应激(CVS)两周后分别在前边缘皮层(PL)、边缘下皮层(IL)和下丘脑室旁核(PVN)中的表达,分别代表了同型和异型方案。没有压力的动物作为对照。我们使用细胞数量和场染色密度对PL和IL的第2层和第3层与第5层和第6层的Iba-1免疫荧光进行了特异性检测。与对照组相比,RR后PL和IL的Iba-1场染色密度均增加。在CVS后没有观察到这种效果。此外,PVN Iba-1免疫反应性不受两种应激方案的影响。细胞数量在任何脑区或压力暴露中都没有变化。小胶质场密度的变化不能反映血管密度的变化。PL和IL小胶质细胞密度的增加表明,在抗炎糖皮质激素作用有限升高的背景下,轻度应激可能导致RR期间选择性的小胶质细胞激活。由NIH资助[MH049698和MH069860]。
Stress pathology is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and aberrant glucocorticoid responses. Recent studies indicate increases in prefrontal cortical ionized calcium-binding adapter molecule 1 (Iba-1) staining following repeated restraint, reflecting increased microglial densities. Our experiments tested expression of Iba-1 staining in the prelimbic cortex (PL), infralimbic cortex (IL) and the hypothalamic paraventricular nucleus (PVN) following two-week exposure to repeated restraint (RR) and chronic variable stress (CVS), representing homotypic and heterotypic regimens, respectively. Unstressed animals served as controls. We specifically examined Iba-1 immunofluorescence in layers 2 and 3 versus layers 5 and 6 of the PL and IL, using both cell number and field staining density. Iba-1 field staining density was increased in both the PL and IL following RR in comparison to controls. This effect was not observed following CVS. Furthermore, PVN Iba-1 immunoreactivity was not affected by either stress regimen. Cell number did not vary within any brain areas or across stress exposures. Changes in microglial field density did not reflect changes in vascular density. Increases in PL and IL microglial density indicate selective microglial activation during RR, perhaps due to mild stress in the context of limited elevations in anti-inflammatory glucocorticoid actions. Supported by NIH grants [MH049698 and MH069860].
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