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Impact of ovariectomy and CO2 inhalation on microglia morphology in select brainstem and hypothalamic areas regulating breathing in female rats
Brain Research ( IF 2.7 ) Pub Date : 2021-01-07 , DOI: 10.1016/j.brainres.2021.147276
Danuzia A Marques 1 , Luciane H Gargaglioni 2 , Vincent Joseph 1 , Frédéric Bretzner 3 , Kênia C Bícego 2 , Stéphanie Fournier 1 , Richard Kinkead 1
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The neural network that regulates breathing shows a significant sexual dimorphism. Ovarian hormones contribute to this distinction as, in rats, ovariectomy reduces the ventilatory response to CO2. Microglia are neuroimmune cells that are sensitive to neuroendocrine changes in their environment. When reacting to challenging conditions, these cells show changes in their morphology that reflect an augmented capacity for producing pro- and anti-inflammatory cytokines. Based on evidence suggesting that microglia contribute to sex-based differences in reflexive responses to hypercapnia, we hypothesized that ovariectomy and hypercapnia promote microglial reactivity in selected brain areas that regulate breathing. We used ionized calcium-binding-adapter molecule-1 (Iba1) immunolabeling to compare the density and morphology of microglia in the locus coeruleus (LC), the caudal medullary raphe, the caudal part of the nucleus of the tractus solitarius (cNTS), and the paraventricular nucleus of the hypothalamus (PVN). Tissue was obtained from SHAM (metaestrus) female rats or following ovariectomy. Rats were exposed to normocapnia or hypercapnia (5% CO2, 30 min). Ovariectomy and hypercapnia did not affect microglial density in any of the structures studied. Ovariectomy promoted a reactive phenotype in the cNTS and LC, as indicated by a larger morphological index. In these structures, hypercapnia had a relatively modest opposing effect; the medullary raphe or the PVN were not affected. We conclude that ovarian hormones attenuate microglial reactivity in CO2/H+ sensing structures. These data suggest that microglia may contribute to neurological diseases in which anomalies of respiratory control are associated with cyclic fluctuations of ovarian hormones or menopause.



中文翻译:


卵巢切除术和二氧化碳吸入对雌性大鼠调节呼吸的特定脑干和下丘脑区域小胶质细胞形态的影响



调节呼吸的神经网络表现出显着的性别二态性。卵巢激素促成了这种区别,因为在大鼠中,卵巢切除术降低了对 CO 2的通气反应。小胶质细胞是对其环境中的神经内分泌变化敏感的神经免疫细胞。当对挑战性条件做出反应时,这些细胞表现出形态变化,反映出产生促炎和抗炎细胞因子的能力增强。基于表明小胶质细胞导致对高碳酸血症的反射反应存在性别差异的证据,我们假设卵巢切除术和高碳酸血症会促进调节呼吸的特定大脑区域的小胶质细胞反应性。我们使用离子钙结合适配器分子 1 (Iba1) 免疫标记来比较蓝斑 (LC)、中缝尾部、孤束核尾部 (cNTS) 中小胶质细胞的密度和形态。和下丘脑室旁核(PVN)。组织取自SHAM(发情后期)雌性大鼠或卵巢切除术后。将大鼠暴露于正常碳酸血症或高碳酸血症(5% CO 2,30分钟)。卵巢切除术和高碳酸血症不会影响任何研究结构中的小胶质细胞密度。更大的形态学指数表明,卵巢切除术促进了 cNTS 和 LC 的反应表型。在这些结构中,高碳酸血症具有相对适度的相反作用。髓缝或 PVN 未受影响。我们得出的结论是,卵巢激素减弱了CO 2 /H +传感结构中小胶质细胞的反应性。 这些数据表明,小胶质细胞可能导致神经系统疾病,其中呼吸控制异常与卵巢激素或更年期的周期性波动有关。

更新日期:2021-01-07
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