Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.
Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.
复制标题
重度抑郁症患者前列腺素 D-2 水平降低与抑郁样行为相关
DOI：
10.1093/ijnp/pyx044
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发表时间：
2017-09-01
期刊：
影响因子：
--
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Chu C;Wei H;Zhu W;Shen Y;Xu Q
前列腺素（PG） D2是哺乳动物大脑中含量最多的前列腺素。PGD2在中枢神经系统中的生理和药理作用似乎与抑郁症患者表现出的一些症状有关。既往研究发现，重度抑郁症患者脑脊液中PGD2合酶降低。我们推测在重度抑郁症中可能存在PGD2水平失调。采用超高效液相色谱-串联质谱联用稳定同位素标记内标法测定重度抑郁症患者血浆和抑郁症小鼠脑内PGD2水平。共招募32名无药物的重度抑郁症患者和30名健康对照者。通过对小鼠进行5周的慢性不可预测的轻度应激，建立了抑郁症动物模型。为探讨PGD2在重度抑郁症中的作用，采用四氯化硒模拟小鼠PGD2水平的变化。在强迫游泳测试中，暴露于慢性不可预测的轻度压力下的小鼠表现出抑郁样行为，表明糖偏好降低和静止时间增加。与对照组相比，重度抑郁症患者血浆和抑郁症小鼠大脑中的PGD2水平均有所下降。进一步抑制小鼠PGD2的产生导致强制游泳试验中静止时间的增加，这可以通过丙咪嗪逆转。重度抑郁症患者PGD2水平降低与抑郁样行为有关。
Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors.
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