Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis.
Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis.
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DOI：
10.1186/s12974-023-02713-0
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发表时间：
2023-03-06
影响因子：
9.3
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中科院分区：
文献类型：
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慢性盆腔疼痛（CPP）是子宫内膜异位症的常见症状。患有子宫内膜异位症的妇女也有患焦虑、抑郁和其他心理障碍的高风险。最近的研究表明，子宫内膜异位症可以影响中枢神经系统（CNS）。在子宫内膜异位症的大鼠和小鼠模型的脑中，已经报道了神经元的功能活性、功能性磁共振成像信号和基因表达的变化。迄今为止，大多数研究都集中在神经元的变化上，而不同脑区的神经胶质细胞的变化尚未得到研究。通过将供体子宫组织同基因转移到受体动物的腹腔中，在雌性小鼠（45日龄; n = 6-11/时间点）中诱导子宫内膜异位症。在诱导后第4、8、16和32天采集脑、脊柱和子宫内膜异位病变进行分析。使用假手术小鼠作为对照（n = 6/时间点）。使用行为测试评估疼痛。在斐济使用小胶质细胞标记物离子化钙结合衔接分子-1（IBA 1）的免疫组织化学和机器学习“Weka可训练分割”插件，我们评估了不同脑区小胶质细胞的形态学变化。还评价了星形胶质细胞的胶质纤维酸性蛋白（GFAP）、肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）的变化。我们观察到在第8、16和32天，与假手术对照组相比，子宫内膜异位症小鼠的皮质、海马、丘脑和下丘脑中的小胶质细胞索马体积增加。与假手术对照组相比，在第16天，患有子宫内膜异位症小鼠的皮质、海马、丘脑和下丘脑中IBA 1和GFAP阳性区域的百分比增加。子宫内膜异位症组和假手术对照组之间的小胶质细胞和星形胶质细胞的数量没有差异。我们观察到增加TNF和IL 6的表达时，表达水平从所有的大脑区域相结合。患有子宫内膜异位症的小鼠在腹部和后爪表现出减少的穴居行为和痛觉过敏。我们相信这是第一个报告中枢神经系统范围内的神经胶质细胞激活的小鼠模型子宫内膜异位症。这些结果对于理解与子宫内膜异位症相关的慢性疼痛和其他问题，如子宫内膜异位症妇女的焦虑和抑郁有着重要的意义。在线版本包含补充材料，可通过10.1186/s12974-023-02713-0获得。
Chronic pelvic pain (CPP) is a common symptom of endometriosis. Women with endometriosis are also at a high risk of suffering from anxiety, depression, and other psychological disorders. Recent studies indicate that endometriosis can affect the central nervous system (CNS). Changes in the functional activity of neurons, functional magnetic resonance imaging signals, and gene expression have been reported in the brains of rat and mouse models of endometriosis. The majority of the studies thus far have focused on neuronal changes, whereas changes in the glial cells in different brain regions have not been studied. Endometriosis was induced in female mice (45-day-old; n = 6–11/timepoint) by syngeneic transfer of donor uterine tissue into the peritoneal cavity of recipient animals. Brains, spines, and endometriotic lesions were collected for analysis at 4, 8, 16, and 32 days post-induction. Sham surgery mice were used as controls (n = 6/timepoint). The pain was assessed using behavioral tests. Using immunohistochemistry for microglia marker ionized calcium-binding adapter molecule-1 (IBA1) and machine learning “Weka trainable segmentation” plugin in Fiji, we evaluated the morphological changes in microglia in different brain regions. Changes in glial fibrillary acidic protein (GFAP) for astrocytes, tumor necrosis factor (TNF), and interleukin-6 (IL6) were also evaluated. We observed an increase in microglial soma size in the cortex, hippocampus, thalamus, and hypothalamus of mice with endometriosis compared to sham controls on days 8, 16, and 32. The percentage of IBA1 and GFAP-positive area was increased in the cortex, hippocampus, thalamus, and hypothalamus in mice with endometriosis compared to sham controls on day 16. The number of microglia and astrocytes did not differ between endometriosis and sham control groups. We observed increased TNF and IL6 expression when expression levels from all brain regions were combined. Mice with endometriosis displayed reduced burrowing behavior and hyperalgesia in the abdomen and hind-paw. We believe this is the first report of central nervous system-wide glial activation in a mouse model of endometriosis. These results have significant implications for understanding chronic pain associated with endometriosis and other issues such as anxiety and depression in women with endometriosis. The online version contains supplementary material available at 10.1186/s12974-023-02713-0.
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影响因子：
13.3
作者：
Brawn J;Morotti M;Zondervan KT;Becker CM;Vincent K
通讯作者：
Vincent K
影响因子：
4
作者：
Bajaj, P;Bajaj, P;Arendt-Nielsen, L
通讯作者：
Arendt-Nielsen, L
影响因子：
5.8
作者：
Arganda-Carreras, Ignacio;Kaynig, Verena;Seung, H. Sebastian
通讯作者：
Seung, H. Sebastian
影响因子：
4.8
作者：
Castro, Joel;Maddern, Jessica;Brierley, Stuart M.
通讯作者：
Brierley, Stuart M.
影响因子：
6.1
作者：
Abbott, JA;Hawe, J;Garry, R
通讯作者：
Garry, R