Sphingosine-1-phosphate receptor 3 in the medial prefrontal cortex promotes stress resilience by reducing inflammatory processes
Sphingosine-1-phosphate receptor 3 in the medial prefrontal cortex promotes stress resilience by reducing inflammatory processes
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DOI：
10.1038/s41467-019-10904-8
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发表时间：
2019-07-17
影响因子：
16.6
通讯作者：
Bhatnagar, Seema
中科院分区：
文献类型：
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作者：
Corbett, Brian F.;Luz, Sandra;Bhatnagar, Seema
压力会促进精神疾病的发展，尽管有些人比其他更有弹性的人更容易受到压力的影响。在这里，我们发现大鼠内侧前额叶皮层 (mPFC) 中的 1-磷酸鞘氨醇受体 3 (S1PR3) 调节对慢性社交失败压力的恢复能力。与易受影响的大鼠和对照大鼠相比，恢复性大鼠的 mPFC 中 S1PR3 表达升高。 mPFC 中病毒介导的 S1PR3 过度表达会产生弹性表型，而其敲除则会产生脆弱表型，其特征是焦虑和抑郁样行为增加，而这些效应是由 TNF α 介导的。此外，我们发现，与暴露于战斗的对照受试者相比，患有 PTSD 的退伍军人血液中的 S1PR3 mRNA 减少，并且其表达与症状严重程度呈负相关。总之，这些数据表明 S1PR3 是应激恢复力的调节剂，并揭示鞘脂受体是与应激相关的精神疾病相关的重要底物。
Stress can promote the development of psychiatric disorders, though some individuals are more vulnerable to stress compared to others who are more resilient. Here we show that the sphingosine-1-phosphate receptor 3 (S1PR3) in the medial prefrontal cortex (mPFC) of rats regulates resilience to chronic social defeat stress. S1PR3 expression is elevated in the mPFC of resilient compared to vulnerable and control rats. Virally-mediated over-expression of S1PR3 in the mPFC produces a resilient phenotype whereas its knock-down produces a vulnerable phenotype, characterized by increased anxiety-and depressive-like behaviors, and these effects are mediated by TNF alpha. Furthermore, we show that S1PR3 mRNA in blood is reduced in veterans with PTSD compared to combat-exposed control subjects and its expression negatively correlates with symptom severity. Together, these data identify S1PR3 as a regulator of stress resilience and reveal sphingolipid receptors as important substrates of relevance to stress-related psychiatric disorders.