Activation of Hypocretin Neurons in Endometriosis.
Activation of Hypocretin Neurons in Endometriosis.
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子宫内膜异位症中下丘脑分泌素神经元的激活。
DOI：
10.1007/s43032-021-00682-4
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Taylor,HughS
中科院分区：
文献类型：
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作者：
Mamillapalli,Ramanaiah;Dang,Tran;Habata,Shutaro;Gao,Xiao-Bing;Taylor,HughS
子宫内膜异位症是一种妇科疾病，影响6-10%的育龄妇女。除了妇科症状外，子宫内膜异位症还伴有各种全身性影响，包括炎症、体重改变和行为改变。先前的鼠类研究表明，子宫内膜异位症与疼痛敏感性增加、行为改变和低体重指数（BMI）有因果关系。可能介导这些发现的一个可能的细胞靶点是下丘脑泌素/食欲素神经元。该神经元系统在调节觉醒/睡眠周期、疼痛感知和食欲方面发挥作用。我们假设子宫内膜异位症改变了下丘脑泌素/食欲素（Hcrt）神经元系统的活性水平。小鼠进行子宫内膜异位症诱导手术（endo）或假手术（sham）以建立实验模型。对从外侧下丘脑收获的样品进行免疫细胞化学，并通过定量在假手术和endo小鼠中急性应激后这些细胞中cAMP反应元件结合蛋白（CREB）的磷酸化表达来检查Hcrt细胞的活化水平。子宫内膜异位症小鼠的Hcrt神经元活化程度高于假手术小鼠。与没有子宫内膜异位症的小鼠相比，用高脂肪饮食喂养的子宫内膜异位症小鼠显示出较低的脂肪/体重和脂肪/瘦肉组织比。假手术组和子宫内膜异位症组小鼠的摄食量无显著差异。这些结果表明，子宫内膜异位症与低体重和下丘脑泌素/食欲素活性增加有关，这可能与行为变化和身体成分的差异有关。
Endometriosis is a gynecological disease affecting 6–10% of women of reproductive age. In addition to gynecologic symptoms, endometriosis is associated with various systemic effects, including inflammation, altered body weight, and behavioral changes. Previous murine studies demonstrate that endometriosis is causally inked to increased pain sensitization, behavioral changes, and low body mass index (BMI). One possible cellular target that may mediate some of these findings is the hypocretin/orexin neurons. This neuronal system plays a role in regulating wakefulness/sleep cycles, pain perception, and appetite. We hypothesize that endometriosis alters activity level of the hypocretin/orexin (Hcrt) neuronal system. Mice underwent endometriosis induction surgeries (endo) or sham surgeries (sham) for the development of the experimental model. Immunocytochemistry was performed on harvested samples from the lateral hypothalamus, and activation levels of Hcrt cells were examined by quantifying the expression of phosphorylation of cAMP-responsive element binding protein (CREB) in these cells after an acute stress in sham and endo mice. Mice with endometriosis had greater Hcrt neurons activation than sham mice. Mice with endometriosis fed with high fat diet showed a lower fat/body weight and fat/lean tissue ratio compared to mice without endometriosis. There was no significant difference in food intake between sham and endometriosis mice. These results demonstrate that endometriosis is associated with low body mass and increased hypocretin/orexin activity, which could be implicated in the behavioral changes and to differences in body composition.