Paricalcitol alleviates lipopolysaccharide-induced depressive-like behavior by suppressing hypothalamic microglia activation and neuroinflammation
Paricalcitol alleviates lipopolysaccharide-induced depressive-like behavior by suppressing hypothalamic microglia activation and neuroinflammation
复制标题
帕立骨化醇通过抑制下丘脑小胶质细胞活化和神经炎症来减轻脂多糖诱导的抑郁样行为
DOI：
10.1016/j.bcp.2019.01.021
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发表时间：
2019-05-01
影响因子：
5.8
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
He, Ming-chao;Shi, Zhe;Zhang, Yan
抑郁症在患有慢性炎症性疾病的患者中非常普遍。神经炎症失调和伴随的小胶质细胞活化在抑郁症的发病机制中起关键作用。Paricalcitol （Pari）是一种维生素D2类似物，已被证明对肾脏和心血管疾病具有抗炎作用。在本研究中，小鼠在通过全身脂多糖（LPS）注射诱导急性抑郁样行为之前，先用Pari进行预处理。为了确定急性体重部分改变的治疗效果，对蔗糖偏好、强迫游泳和悬尾试验进行了评估。然后，研究了参与抑郁症病理生理的下丘脑促炎症细胞因子il - 1- β水平和小胶质细胞活性的变化。结果表明，Pari可显著缓解全身LPS注射诱导的抑郁样行为，表现为增加蔗糖偏好，降低TST和FST的不动性。Pari可特异性调节小胶质细胞介导的神经炎症过程和肾素-血管紧张素系统的局部活性，发挥其抗抑郁作用。这项研究表明，特立西醇在治疗全身性炎症引起的抑郁症状，特别是慢性高血压患者中的潜力。
Depression is highly prevalent in patients suffering from chronic inflammatory diseases. Dysregulated neuroinflammation and concomitant activated microglia play a pivotal role in the pathogenesis of depression. Paricalcitol (Pari), a vitamin D2 analogue, has been demonstrated to exert anti-inflammative effects on renal and cardiovascular diseases. In this study, mice were pretreated with Pari before being induced to acute depression-like behaviors by systemic lipopolysaccharide (LPS) injection. To determine the therapeutic effects of Part alterations in acute body weight, sucrose preference, forced swimming and tail suspension tests were assessed. Then, alterations of pro-inflammation cytokine IL1-beta level and microglia activity in the hypothalamus, which are involved in the pathophysiology of depression, were examined. The results showed that Pari significantly alleviated systemic LPS injection induced depressive-like behaviors as shown by increased sucrose preference and decreased TST and FST immobility. Pari could specifically regulate microglia-mediated neuroinflammation process and local activity of renin-angiotensin system to exert its anti-depressant effects. This study demonstrated a potential for paricalcitol in treating depressive symptoms induced by systemic inflammation, particularly in patients with chronic hypertension.